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RARA (Retinoic acid receptor, alpha)

Written2000-10Franck Vigué
Laboratoire de Cytogénétique - Service d'Hématologie Biologique, Hôpital Hôtel-Dieu - 75181 Paris Cedex 04, France
Updated2020-03Franck Vigué
franck.viguie@free.fr

Abstract Review on RARA with data on DNA, on the protein encoded, and where the gene is implicated.

Keywords RARA; Retinoic acid receptor, alpha; Acute promyelocytic leukaemia; M3-AML

(Note : for Links provided by Atlas : click)

Identity

Alias_namesretinoic acid receptor, alpha
Alias_symbol (synonym)RAR
NR1B1
Other aliasNuclear Receptor Subfamily 1 Group B Member 1
Nucleophosmin-Retinoic Acid Receptor Alpha Fusion
HGNC (Hugo) RARA
LocusID (NCBI) 5914
Atlas_Id 46
Location 17q21.2  [Link to chromosome band 17q21]
Location_base_pair Starts at 40318221 and ends at 40357643 bp from pter ( according to hg19-Feb_2009)  [Mapping RARA.png]
 
  c-RARA (17q21) in normal cells: PAC 833D9 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
 
  RARA (Retinoic acid receptor, alpha) Hybridization with LSI RARA Dual Color, Break Apart Rearrangement Probe (Abbott Molecular, US), showing the RARA gene on 17q21.2 (red-green or a fused yellow signal - Courtesy Adriana Zamecnikova.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BCOR (Xp11.4) / RARA (17q21.2)CELF2 (10p14) / RARA (17q21.2)ETV6 (12p13.2) / RARA (17q21.2)
FIP1L1 (4q12) / RARA (17q21.2)GTF2I (7q11.23) / RARA (17q21.2)H2AFV (7p13) / RARA (17q21.2)
IRF2BP2 (1q42.3) / RARA (17q21.2)KMT2A (11q23.3) / RARA (17q21.2)NABP1 (2q32.3) / RARA (17q21.2)
NPM1 (5q35.1) / RARA (17q21.2)NUMA1 (11q13.4) / RARA (17q21.2)PML (15q24.1) / RARA (17q21.2)
PRKAR1A (17q24.2) / RARA (17q21.2)RARA (17q21.2) / BRD4 (19p13.12)RARA (17q21.2) / CA10 (17q21.33)
RARA (17q21.2) / CDC6 (17q21.2)RARA (17q21.2) / CDK12 (17q12)RARA (17q21.2) / COL10A1 (6q22.1)
RARA (17q21.2) / HOXB3 (17q21.32)RARA (17q21.2) / KMT2A (11q23.3)RARA (17q21.2) / MSL1 (17q21.1)
RARA (17q21.2) / MYO1D (17q11.2)RARA (17q21.2) / NARS2 (11q14.1)RARA (17q21.2) / NPM1 (5q35.1)
RARA (17q21.2) / NUMA1 (11q13.4)RARA (17q21.2) / PCTP (17q22)RARA (17q21.2) / PGAP3 (17q12)
RARA (17q21.2) / PKIA (8q21.12)RARA (17q21.2) / PML (15q24.1)RARA (17q21.2) / POLDIP2 (17q11.2)
RARA (17q21.2) / PRKAR1A (17q24.2)RARA (17q21.2) / PRR11 (17q22)RARA (17q21.2) / PSMD3 (17q21.1)
RARA (17q21.2) / RARA (17q21.2)RARA (17q21.2) / RP11-1407O15.2 ()RARA (17q21.2) / SKAP1 (17q21.32)
RARA (17q21.2) / STAC2 (17q12)RARA (17q21.2) / STAT3 (17q21.2)RARA (17q21.2) / STAT5B (17q21.2)
RARA (17q21.2) / TIF1 ()RARA (17q21.2) / TMEM94 (17q25.1)RARA (17q21.2) / TRIM24 (7q33)
RARA (17q21.2) / WIPF2 (17q21.1)RARA (17q21.2) / ZBTB16 (11q23.2)RARA (17q21.2) / ZNF145 ()
RARA (17q21.2) / ZNF595 (4p16.3)SNU13 (22q13.2) / RARA (17q21.2)STAT5A (17q21.2) / RARA (17q21.2)
STAT5B (17q21.2) / RARA (17q21.2)TAOK1 (17q11.2) / RARA (17q21.2)TBL1XR1 (3q26.32) / RARA (17q21.2)
TMEM11 (17p11.2) / RARA (17q21.2)TPCN2 (11q13.3) / RARA (17q21.2)TRIM24 (7q33) / RARA (17q21.2)
ZBTB16 (11q23.2) / RARA (17q21.2)

DNA/RNA

Description 9 exons; total gene sequence: 7450 bp.
Transcription 2.8 and 3.6 kb transcripts.

Protein

 
  RARA protein and domains.
Description 462 amino acids - 6 evolutionarily conserved domains - 5 functional domains : N-terminal A/B domain (transcriptional regulation AF1), C (DNA binding domain, contains 2 zinc fingers motifs, necessary for binding to RARE DNA sequence), D (cellular localization signal), E (ligand-binding domain, transcriptional regulation AF2) and F (function not well understood today)..
Expression RARA is expressed in hematopoietic cells.
Localisation Nuclear localisation.
 
  Retinoid structures.
Function Ligand-dependent transcription factor activated by all-trans retinoic acid (ATRA), specifically involved in hematopoietic stem cells differentiation and maturation = receptor for all-trans retinoic acid (ATRA) and 9-cis RA which are intracellular metabolites of vitamine A, active in cellular differentiation and morphogenesis. The gene response to RARA binding is modulated by a series of co-repressors and co-activators.
Retinol (vitamin A) is strictly furnished by the nutrition. The active retinol product is the retinoic acid (RA) which plays a great role as modulator of proliferation and differentiation in numerous tissues. In target cells retinol is oxidized as retinal with the help of an alcohol dehydrogenase. Then retinal is oxidized as ATRA by a retinal dehydrogenase (ALDH1A2 or RALDH). ATRA gives rise to 9-cis-RA, 11-cis-RA and 13-cis-RA, via an isomerase. All these isoforms are members of the retinoids, acting in different tissues after linkage with specific nuclear protein receptors. There are two families of RA receptors, the RARs (retinoic acid receptor α, β, and γ: RARA, RARB, RARG) and the RXRs (retinoid X receptor α, β and γ: RXRA, RXRB, RXRG). RARA (RARα) is involved essentially in hematopoiesis, while RARγ (RARG) is assigned to the skin. To be activated RARs can bind to ATRA or 9-cis-RA while RXRs bind only to 9-cis-RA (Allenby G et al., 1993).
Wild type RARA binds to DNA by its C domain, as a heterodimer with a related retinoid X receptor (RXR). The site of binding is a specific DNA sequence, the RA response element (RARE). The RARE domain is located in the promoter of target genes, it is composed classically of two direct repeats of a consensus sequence 5'-PuG(G/T)CA-3', separated by 1, 2 or 5 base pairs named respectively DR1, DR2 and DR5 (Umesono K et al., 1991). In the absence of ligand the AF2 domain of the RARA protein associates with corepressors NCOR2 (also called SMRT: silencing mediator of retinoid thyroid hormones) and/or N-CoR (nuclear corepressor) which are members of a multiprotein repressor complex. In this complex SMRT and N-Cor associate with the Sin3 proteins (SIN3A and SIN3B) which then links to histone deacetylases HDAC1 and/or HDAC2. Histone deacetylation would produce a local structural modification of the chromatin with an arrest of transcription initiation (Beato M et al., 1995; Pazin MJ and Kadonaga JT, 1997; Melnick A and Licht JD, 1999).
Transport of the ligands ATRA and 9-cis-RA, and their link with RAR/RXR heterodimer are facilitated by another family of receptors, CRABP1 and CRABP2 (cellular retinoic acid binding proteins) (Bastie JN et al., 2001).
When the ligand reaches its target it binds to RARA on the AF2 domain and modifies the molecular conformation of the receptor, so that the repressor complex dissociates from the molecule and is replaced by coactivator proteins which can bind at the same site (Chambon P, 1996; Wade PA and Wolffe AP, 1997). These coactivators involve TRIM24 (also called TIF1), PSMC5 (also called TRIP1 or SUG1), NCOA2 (TIF2), NCOA3 (ACTR), NCOA1 (SRC-1), TAF4 (TAFII135), and CREBBP (CBP). PSMC5 has a DNA helicase activity, able to unwind DNA. CREBBP and NCOA3 have an histone acetylase activity, they bind to KAT2B (P/CAF) which is also an histone acetylase. Consequently, when RARA binds to its ligand ATRA, it becomes the member of a multiprotein complex, in association with RXR and a number of coactivators. The result is a local histone reacetylation leading to the modification of chromatin conformation and stimulation of transcription machinery.
The activity of many genes involved in myeloid maturation, including transcription factors, may be potentially triggered by this coactivator's complex, resulting in the arrest of cell growth, terminal differentiation and production of mature granulocytes.
Homology RARA shares homology with RARB and RARG, 9-cis RA receptors (RXRs) and receptors for thyroid and steroid hormones and for vitamine D3 ( VDR)

Implicated in

Note In oncogenesis, RARA has been primarily implicated in acute promyelocytic leukaemia (APL) induction, via the expression of the PML/RARA fusion gene. Apart from its fusion with PML, RARA gene may be seldom fused by translocation, with a great variety of genes (Chen Z et al., 1996; Redner RL, 2002; Adams J and Nassiri M, 2015; Yan W and Zhang G, 2016) and all these fusion genes contain the RARA C-terminal B through F domains, encoding DNA binding, retinoid X receptor (RXR) heterodimerization, ligand binding, and co-repressor and co-activator interaction functions of RARA, leading invariably and specifically to the development of an APL. In all the variant translocations the functional activity of PML is not altered showing the crucial role of RARA in the leukemogenesis process. On other part it was observed recently that RARB or RARG, instead of RARA, could exceptionally fuse with various genes, giving rise to an APL responding poorly to ATRA therapy (Osumi T et al., 2018; Miller CA et al.; 2018; Chen X et al., 2019)
  
Entity t(15;17)(q24;q21) / acute promyelocytic leukemia (APL) --> PML / RARA
Note The translocation fuses the promyelocytic leukaemia gene (PML) at 15q24 with RARA (Kakizuka A et al., 1991; de Thé H et al., 1991).
Disease Typical APL (or M3 AML, FAB classification), approximately 98% of APL cases; arrest of the white blood cells maturation at the promyelocytic stage giving an accumulation of abnormal promyelocytes with Auer rods and bundles (faggots); disruption of the PODs with a microspeckeled pattern; maturation response to all-trans retinoic acid (ATRA) therapy.
Prognosis Immediate prognosis is impaired by intravascular disseminated coagulopathy; long term prognosis is favorable with treatment combining ATRA and/or arsenic trioxide (ATO) plus anthracycline chemotherapy (Wang Z-Y and Chen Z, 2008; Testa U and Lo-Coco F, 2016).
Treatment: More than 90% of complete remission with ATRA plus ATO. Additional gene(s) alterations, involving mainly FLT3, KRAS or CMYC, are considered as progression factors (de Thé H, 2018).
Cytogenetics Variant or complex t(15;17) translocation in 5% of cases, no known prognosis implication; secondary chromosomal abnormalities in 30 to 35% of APL at diagnosis; association with +8 in 17 to 28% of cases; other associations are rare but recurrent: del(7q), del(9q), ider(17)t(15;17), +21. Rarely the t(15;17) is not detectable cytogenetically, resulting from a cryptic molecular insertion; if the insertion is too small, FISH analysis may be negative and the molecular analysis only will be able to detect the PML-RARA transcripts.
Hybrid/Mutated Gene The crucial fusion transcript is 5'PML-3'RARA, encoded by der(15) chromosome; the counterpart 5'RARA-3'PML encoded by der(17) is inconstant.
The breakpoint in RARA gene is always located in intron between A and B domains.
PML gene is composed of approximately 53.000 bp with 9 exons; the PML protein is member of a multiprotein complex composing the matrix-associated nuclear bodies, which are dynamic nuclear components of 0.1 to 1.0 m in size. PML works as a tumour suppressor gene, the protein is implicated in a wide variety of cellular functions: apoptosis, differentiation, genome stability (Bernardi R and Pandolfi PP, 2007; Hsu K-S and Kao H-Y, 2018). There are three breakpoint clusters in PML gene: bcr1 (70% of patients), bcr2 (10%) and bcr3 (20%), giving rise respectively to the long (L), intermediate (V) and short (S) length hybrid PML-RARA transcripts; in the 3 types of proteins the coiled-coil domain of PML, which is an element of the ring-B box-CC/tripartite domain, is conserved; V form would be linked to ATRA with a decreased sensitivity and S form would be associated to an excess of secondary chromosome changes.
Abnormal Protein 106 Kda fusion protein; role in the leukemogenic process through two main pathways: 1) interference with the signalling pathway controlled by RARA and involved in differentiation and maturation of myeloid precursors (mainly dysregulation of retinoid-inducible genes responsible for in myeloid differentiation). 2) disruption of the PML nuclear bodies (PML-NBs) which control the P53 pathway and many other cellular functions involved in genome stability, apoptosis, cellular senescence, differentiation, angiogenesis.
In contrast with wild type RARA which only forms heterodimers with RXRA, the fusion protein PML/RARA can form homodimers through the coiled-coil domain of PML, which is the critical domain for the transformation of PML/RARA into an oncoprotein (Lin RJ and Evans RM, 2000; Occhionorelli M et al., 2011). The homodimer can link to the DNA, independently from RXR. The expression of PML/RARA homodimer is sufficient ex vivo to operate the cellular transformation, however the PML/RARA homodimer is quasi always linked in vivo to RXRA which is necessary to an efficient DNA binding. It results in a dominant negative control of both native PML and RARA functions (de Thé H et al., 1991; Melnick A and Licht JD, 1999; Occhionorelli M et al., 2011). Binding of the homodimer, by the RARA domain of PML-RARA, with DNA sites located in the promoter region of target genes, and multimerisation owing to the coiled-coil domain of PML, enhances the recruitment of co repressor proteins and of histone deacetylases (HDACs), leading to a gene repression via DNA methylation (Di Croce L et al., 2002; Martens JH et al., 2010; Occhionorelli M et al., 2011). The classical consequences are a block of myeloid differentiation at the promyelocytic stage. A second activity of PML-RARA is to disrupts the PML nuclear-bodies involved in many cellular regulations, particularly TP53 activation, leading to an increase of progenitors self renewal (Bernardi R and Pandolfi PP, 2007; Nasr R et al., 2008).
 
Molecular pathogenesis of APL.
  
  
Entity t(11;17)(q23;q12) / acute promyelocytic leukemia --> ZBTB16 / RARA
Note Described in Chen Z et al., 1994; Licht JD et al., 1995; Melnick A and Licht JD, 1999; Sainty D et al., 2000. ZBTB16 is also named PLZF, ZNF145.
Disease Variant acute promyelocytic leukemia (APL) form with atypical cytologic aspects: intermediate morphology between M2 and M3, less or not bilobed promyelocyte nucleus, no Auer rods, the hypogranular form is predominant with coarse granules, absence of faggot cells, increased number of hypogranular pseudo-Pelger neutrophils and increased CD56 expression; generally no response to ATRA therapy; however some cases achieved a remission with a treatment combining ATRA and chemotherapy or ATRA and G-CSF; worse prognostic than APL with t(15;17), whatever the treatment. Found in less than 1% of APL cases.
Cytogenetics In some cases the translocation may be cryptic.
Hybrid/Mutated Gene Native ZBTB16 (zinc finger and BTB domain containing 16) has 7 exons, 3 alternative transcripts; encodes a 673 amino acids zinc finger protein, containing one N-terminal POZ-BTB domain (Pox virus and Zinc finger domain also called Broad Complex, tramtrack, Bric a Brac ), one RD2 domain and 9 C-terminal zinc finger motifs. The native protein is involved as transcriptional repressor in a number of pathways during development (Liu et al., 2016). The t(11;17) results in two reciprocal transcripts, encoding in the same reading frame ZBTB16/RARA and RARA/ZBTB16 proteins. ZBTB16/RARA contains the same RARA domains as in PML/RARA.
Resistance to ATRA therapy is caused by the insensibility to ATRA of the corepressors-ZBTB16-/RARA complex, in which N-CoR/SMRT co repressor proteins maintain there link with the ZBTB16 part of ZBTB16/RARA, even with therapeutic levels of ATRA.
  
  
Entity t(5;17)(q35;q12) / acute promyelocytic leukemia --> NPM1 / RARA
Note Described in Corey SJ et al., 1994; Redner RL et al., 1996; Rush EA et al., 2013. The translocation fuses the nucleophosmin gene (NPM1) with RARA. It is the second most frequent variant translocation after the t(11;17)(q23;q21). Apart from NPM1/RARA two other translocation / fusion gene involve NPM1 in haematological neoplasms: t(2;5)(p23;q35) NPM1/ALK fusion in anaplastic large cell lymphoma and t(3;5)(q25;q35) NPM1/MLF1 fusion in MDS and AML. Down or up regulation of NPM1 caused by mutations lead also to solid tumors (Grisendi S et al., 2006).
Disease Exceptional; expresses overall similar morphologic and immunophenotypic features as classical APL; respond to ATRA treatment.
Hybrid/Mutated Gene NPM1 encodes a nucleolar phosphoprotein mainly involved in ribosomal particles assembly and regulation of centrosome duplication. It is also implicated in the regulation of stability and activity of various tumor suppressor proteins, including TP53. It plays a crucial role in cell growth regulation and genomic stability. According to the physiological or physiopathological conditions NPM1 should be considered either as an oncoprotein or as a tumor suppressor (Grisendi S et al., 2006). The t(5;17) produces both NPM1/RARA and, inconstantly, RARA/NPM1 transcripts. Only NPM1/RARA protein is responsible for APL disease. As for PML/RARA and ZBTB16/RARA fusion genes the breakpoint in RARA occurs in the second intron so that its B-F domain is fused to the N-terminal domains of NPM1, in the same reading frame. The analysis of the initial published case (Redner RL et al., 1996) showed two different breakpoint in NPM1, generating two transcripts of 2.3 kb and 2.4 kb. Both coded two proteins of 520 and 563 amino acids respectively, with the same level of expression. These two fusion proteins had a RA-dependent transcriptional activity.
  
  
Entity t(11;17)(q13;q12) / acute promyelocytic leukemia --> NUMA1 / RARA
Note Described in Wells RA et al., 1996, 1997, the third variant translocation to be described. Only one case reported to date, in a 6-month old male infant.
Disease Presentation as a quite classical APL who expressed, however, multiple unexpected cutaneous lesions but peripheral blood smears and cellular immunophenotype were typical of APL. Respond to ATRA treatment and there was no relapse at 3 years after autologous bone marrow transplantation.
Hybrid/Mutated Gene The NUMA1 gene (nuclear mitotic apparatus) located at 11q13, encodes NuMA, a high molecular weight (238 kDa) coiled-coil protein component of the nuclear matrix at interphase and associated with the spindle poles during mitosis. It is involved in the processes of mitosis and in the nuclear reconstructing after mitosis. NUMA1 is composed of a large coiled-col interstitial domain of approximately 1500 amino acids involved in homo-heterodimerization, encompassed with two globular C-terminal and N-terminal domains. The C-terminal domain contains a nuclear localization signal (NLS), a microtubule binding domain (MT), a LGN binding sequence and 4 phosphorylation sites. This complex domain is necessary for localization to the nucleus and mitotic spindle functioning. The N-terminal domain is required for post mitotic nuclear reassociation. Both N- and C-terminal domains contain DNA-binding S/TPXX motifs (Melnick A and Licht JD, 1999; Radulescu AE and Cleveland DW, 2010).
The t(11;17)(q13;q21) gave rise to a 2286 amino acids NUMA1/RARA fusion protein, linking in the same reading frame the B-F domain of RARA to the N-terminal globular and the coiled coil domains of NUMA1. No alternative RARA/ NUMA1 protein could be detected. NUMA1/RARA plays a role of dominant negative RA receptor. It is able to bind to quite the same RARE sites as PML/RARA, equally as a homodimer or a heterodimer with RXR but more stable as a RXR heterodimeric complex (Dong S et al., 2003).
  
  
Entity der(17) / acute promyelocytic leukemia --> STAT5B / RARA
Note The STAT5B/RARA fusion gene is a rare event, no more than 12 cases were published in 2018. It results probably from a variable rearrangement of 17q, interstitial deletion, duplication, inversion or other more complex rearrangement, undetectable by conventional and molecular cytogenetic. However FISH with a commercial RARA dual colour or break apart probe is able sometimes to give informations, mainly in case of deletion of the 3'-RARA sequences. In the first published case (Arnould C et al., 1999) der(17) resulted from a duplication of the 17q21.3-q23 segment.
Disease Male predominance, only two female cases reported. Clinical and cytological data compatibles with variant APL or sometimes quite atypical for APL. Very poor response to ATRA and/or ATO therapy. No one long term complete remission could be obtained (Zang C et al., 2018).
Hybrid/Mutated Gene The STAT5B gene (signal transducer and activator of transcription 5B) is located at 17q21.2, it contains 19 exons and a total of 5090 coding nucleotides. It is a member of the STAT family, it encodes a 92 kD S STAT5B protein which contains STAT proteins conserved domains: a N- terminal coiled coil domain, a DNA binding domain, a SH2 domain and a C-terminal transactivation domain. STAT5B is a signal transducer and activator of transcription, acting in the janus kinase (JAK)-STAT signaling pathway. It is activated by tyrosine-phosphorylation, permitting homo- or heteridimerization. Located inactive in the cytoplasm, the protein is rapidly translocated to the nucleus after dimerization and binds to DNA to activate its target genes (Del Rosario AM et al., 2012).
The STAT5B/RARA fusion protein is composed of the N- terminal coiled-coil domain necessary for dimerization, the DNA binding domain, the SH2 and a part of the SH3 domains of STAT5B, fused in the same reading frame to the B to F domains of RARA. No alterne RARA/ STAT5B protein is produced. Like PML/RARA, STAT5B /RARA binds to RARE as a homodimer or heterodimer with RXR. It works as a competitive inhibitor of transcriptional activity of RARA-RXR. This inhibition depends essentially on the presence of the coiled coil domain of STAT5B. When this domain is absent, in transfection experiments with modified STAT5B /RARA protein, STAT5B/RARA expresses the same transcriptional activity as wild type RARA (Dong S and Tweardy DJ, 2002; Huret JL, 2010).
  
  
Entity t(X;17) (p11;q21) / acute promyelocytic leukemia --> BCOR / RARA
Note Described in Yamamoto Y et al., 2000. Only two cases reported to date, the first in a 45-year-old man with a 45,-Y, t(X;17)(p11;q21) karyotype.
Disease First case clinical presentation as a variant APL, with 83% of promyelocytes in a hypercellular bone marrow and a coagulopathy, but with unusual rectangular and round cytoplasmic inclusion bodies in promyelocytes. Patient responded to ATRA therapy but was resistant to ATO.
Hybrid/Mutated Gene The BCOR gene (BCL6 co repressor) located at Xp11.4 encodes a 180 kDa nuclear protein which is a component of a polycomb complex acting as a transcription suppressor. The BCOR/RARA fusion protein has a self association capacity through its BCOR-S region and ankyrin-repeat domain. It can also form a heterodimer with RXR to bind with RARE, acting as a dominant negative factor of RARA transcription.
  
  
Entity der(17) / acute promyelocytic leukemia --> PRKAR1A / RARA
Note Described in Catalano A et al., 2007. Only one case published in a 66-year-old man. Karyotype showed only a trisomy 22. RARA break apart FISH showed a deletion of the 5'-RARA probe on a der(17). A dual colour PML/RARA FISH showed a split of the RARA signal on der(17) and normal PML signals. Later on FISH with RARA and PRKAR1A probes confirmed the split of RARA and the PRKAR1A/RARA fusion on the der(17).
Disease The patient was investigated for fatigue and anorexia. No signs of coagulopathy were observed, hypercellular bone marrow contained 83% of hypergranular promyelocytes, but without Auer rods or fagot cells. Patient responded well to ATRA and ATO.
Hybrid/Mutated Gene PRKAR1A (protein kinase A regulatory subunit1) is located at 17q24.2. The protein is involved in the regulation of cAMP-dependent PRKA enzymatic activity. PRKAR1A/RARA binds to a number of RARE sequences, either as a homodimer or as a heterodimer with RXR. However, only the interaction of RXR with PRKAR1A/RARA is critical for leukemic transformation (Qiu JJ et al., 2010).
  
  
Entity t(4;17)(q12;q21) / acute promyelocytic leukemia --> FIP1L1 / RARA
Note Described in Kondo T et al., 2008, Zamecnikova A, 2015. Seventh variant translocation to be described, three APL cases published, however the FIP1L1/RARA fusion was previously reported in one case of juvenile myelomonocytic leukaemia (Buijs A and Bruin M, 2007).
Disease The first patient, a 90-year old woman, responded to ATRA therapy.
Hybrid/Mutated Gene RARA breakpoint was, as expected, up side of exon 3 and it fused with exon 15 or exon 13 of FIP1 motif.
  
  
Entity der (2)t(2;17)(q32;q21) / acute promyelocytic leukemia --> NABP1 / RARA
Note Described in Won D et al., 2013; Zamecnikova A, 2018.
Disease Only one case described to date, a 59-year old man who achieved complete remission with ATRA followed by chemotherapy and allogenic bone marrow stem cells transplantation.
Hybrid/Mutated Gene NABP1 (nucleic acid binding protein 1) also named OBFC2A (oligonucleotides / oligosaccharide binding fold containing 2A) is located at 2q32.3, it is involved in DNA damage response and genome stability. In the NABP1/RARA fusion gene exon 5 of the NABP1 gene is fused with the exon 3 of RARA.
  
  
Entity t(3;17)(26;q21) --> TBL1XR1 / RARA
Note Described in Chen Y et al., 2014; Zamecnikova A, 2018.
Disease Fusion gene detected in a patient with a complex translocation t(3;17)(q26;q21), t(7;17)(q11.2;q21). Three cases known to date. Response to ATRA therapy.
Hybrid/Mutated Gene TBL1XR1/RARA (transducin beta-like 1 X-linked receptor 1) also known as TBLR1 (transducin beta-like protein 1-related protein). The TBL1XR1protein contains a LisH domain which is necessary for homo or heterodimerization, it could be involved in the TBL1XR1/RARA homodimerization.
  
  
Entity t(1;17)(q42;q21) --> IRF2BP2 /RARA
Note Described in Yin CC et al., 2015 ; Shimomura Y et al., 2016 ; Jovanovic JV et al., 2017 ; Zamecnikova A, 2017 ; Mazharuddin S et al., 2018.
Disease Four cases described in 2018, all with clinical, cytological and immunophenotypic features compatibles with APL. Two patients at least responded to ATRA therapy.
Hybrid/Mutated Gene Breakpoint in IRF2BP2 (interferon regulatory factor 2 binding protein 2) exon 2 and in RARA intron 2.
  
  
Entity t(7;17)(q11;q21) --> GTF2I / RARA
Note Described in Li J et al., 2015.
Disease One case reported in a 35-year-old APL man which did not respond to ATRA therapy.
Prognosis In APL, resistance to ATRA was studied on GTF2I/RARA-transfected HL60 cells. It showed that the resistance was associated to the interaction between GTF2I/RARA and the RING finger protein 8 (RFN8) (Yan W et al., 2019).
Hybrid/Mutated Gene The t(7;17) unbalanced translocation resulted in a fusion between exon 6 of GTF2I and common exon 3 of RARA. GTF2I protein (general transcription factor 2I) is a members of the transcription factor 2I family. It contains a leucine zipper for homodimerization and a DNA binding domain. There are 4 human GTF2I isoforms which are expressed in various tissues.
  
  
Entity t(3;17)(q26;q21) --> FNDC3B / RARA
Note Described in Cheng CK et al., 2017.
Disease One case in a 36-year-old man. Cytology and immunophenotype were compatible with APL and patient responded to ATRA followed by chemotherapy and a complete remission was obtained at day 30, however patient relapsed at 8 months.
Hybrid/Mutated Gene At the karyotypic level the translocation was the same as the t(3;17)(26;q21) which produce the TBLR1XR1/RARA fusion. DNA sequencing showed the FNDC3B/RARA fusion between exon 24 of FNDC3B and exon3 of RARA. Two reciprocal RARA-FNDC3B transcripts were detected. FNDC3B (fibronectin type III domain containing 3B) is implicated in protein interactions, particularly it has a role in granulocytic differentiation and it was involved in an APL-like leukaemia without RARA intervention (Wang HY et al., 2016)
  
  
Entity t(3;17)(q12;q21) --> TFG / RARA
Note Described in Chong ML et al., 2018.
Disease One case published in a 16-year-old man with a t(3;14;17) complex translocation. Bone marrow hypergranular promyelocytes and immunophenotype diagnosed an APL which responded to ATRA therapy.
Hybrid/Mutated Gene RNA and cDNA sequencing showed a TFG/RARA fusion. TFG (TRK-fused gene) is located at 3q12.2, breakpoints of the fusion gene occurred in TFG exon 7 and RARA exon 3.
  
  
Entity Non APL malignancies
Disease Mutations in the ligand binding domain of RARA, associated with MED12 gene mutations, were frequently observed in breast fibroadenoma and phyllode tumors (Tan J et al., 2015).
A super enhancer (SE) was observed at the RARA locus, in a subset of patients with AML other than APL. This SE was associated with a high RARA expression and evidences of differentiation in AML cell lines, leading to the hypothesis that non-APL AML patients with such a SE could be sensitive to RA therapy (McKeown MR et al.; 2017).
t(11;17)(q23;q12) / M5 acute myeloid leukemia --> KMT2A / RARA 1 case to date (Shekhter-Levin et al.2000); not found in APL; belongs to the MLL/11q23 leukemias
  

Breakpoints

 

Bibliography

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations
Adams J, Nassiri M
Arch Pathol Lab Med 2015 Oct;139(10):1308-13
PMID 26414475
 
Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids
Allenby G, Bocquel MT, Saunders M, Kazmer S, Speck J, Rosenberger M, Lovey A, Kastner P, Grippo JF, Chambon P, et al
Proc Natl Acad Sci U S A 1993 Jan 1;90(1):30-4
PMID 8380496
 
The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia
Arnould C, Philippe C, Bourdon V, Gr goire MJ, Berger R, Jonveaux P
Hum Mol Genet 1999 Sep;8(9):1741-9
PMID 10441338
 
The novel co-activator CRABPII binds to RARalpha and RXRalpha via two nuclear receptor interacting domains and does not require the AF-2 'core'
Bastie JN, Despouy G, Balitrand N, Rochette-Egly C, Chomienne C, Delva L
FEBS Lett 2001 Oct 19;507(1):67-73
PMID 11682061
 
Steroid hormone receptors: many actors in search of a plot
Beato M, Herrlich P, Schütz G
Cell 1995 Dec 15;83(6):851-7
PMID 8521509
 
Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies
Bernardi R, Pandolfi PP
Nat Rev Mol Cell Biol 2007 Dec;8(12):1006-16
PMID 17928811
 
Fusion of FIP1L1 and RARA as a result of a novel t(4;17)(q12;q21) in a case of juvenile myelomonocytic leukemia
Buijs A, Bruin M
Leukemia 2007 May;21(5):1104-8
PMID 17301809
 
The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia
Catalano A, Dawson MA, Somana K, Opat S, Schwarer A, Campbell LJ, Iland H
Blood 2007 Dec 1;110(12):4073-6
PMID 17712046
 
Deletions in chromosome 6p22
Celestino-Soper PB, Skinner C, Schroer R, Eng P, Shenai J, Nowaczyk MM, Terespolsky D, Cushing D, Patel GS, Immken L, Willis A, Wiszniewska J, Matalon R, Rosenfeld JA, Stevenson RE, Kang SH, Cheung SW, Beaudet AL, Stankiewicz P
3-p24 3, including ATXN1, are associated with developmental delay and autism spectrum disorders
PMID 22480366
 
A decade of molecular biology of retinoic acid receptors
Chambon P
FASEB J 1996 Jul;10(9):940-54
PMID 8801176
 
Long non-coding RNAs: crucial regulators of gastrointestinal cancer cell proliferation
Chen J, Liu S, Hu X
Cell Death Discov 2018 Apr 27;4:50
PMID 29736267
 
A novel NPM1-RARG-NPM1 chimeric fusion in acute myeloid leukaemia resembling acute promyelocytic leukaemia but resistant to all-trans retinoic acid and arsenic trioxide
Chen X, Wang F, Zhang Y, Teng W, Cao P, Ma X, Liu M, Tian Y, Wang T, Nie D, Zhang J, Liu H, Wang W
Br J Cancer 2019 May;120(11):1023-1025
PMID 30996344
 
TBLR1 fuses to retinoid acid receptor α in a variant t(3;17)(q26;q21) translocation of acute promyelocytic leukemia
Chen Y, Li S, Zhou C, Li C, Ru K, Rao Q, Xing H, Tian Z, Tang K, Mi Y, Wang B, Wang M, Wang J
Blood 2014 Aug 7;124(6):936-45
PMID 24782508
 
PLZF-RAR alpha fusion proteins generated from the variant t(11;17)(q23;q21) translocation in acute promyelocytic leukemia inhibit ligand-dependent transactivation of wild-type retinoic acid receptors
Chen Z, Guidez F, Rousselot P, Agadir A, Chen SJ, Wang ZY, Degos L, Zelent A, Waxman S, Chomienne C
Proc Natl Acad Sci U S A 1994 Feb 1;91(3):1178-82
PMID 8302850
 
Retinoic acid regulatory pathways, chromosomal translocations, and acute promyelocytic leukemia
Chen Z, Tong JH, Dong S, Zhu J, Wang ZY, Chen SJ
Genes Chromosomes Cancer 1996 Mar;15(3):147-56
PMID 8721678
 
FNDC3B is another novel partner fused to RARA in the t(3;17)(q26;q21) variant of acute promyelocytic leukemia
Cheng CK, Wang AZ, Wong THY, Wan TSK, Cheung JS, Raghupathy R, Chan NPH, Ng MHL
Blood 2017 May 11;129(19):2705-2709
PMID 28314734
 
Direct and biochemical interaction between dopamine D3 receptor and elongation factor-1Bbetagamma
Cho DI, Oak MH, Yang HJ, Choi HK, Janssen GM, Kim KM
Life Sci 2003 Oct 24;73(23):2991-3004
PMID 14519448
 
Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains
Cho HY, Maeng SJ, Cho HJ, Choi YS, Chung JM, Lee S, Kim HK, Kim JH, Eom CY, Kim YG, Guo M, Jung HS, Kang BS, Kim S
J Biol Chem 2015 Dec 4;290(49):29313-28
PMID 26472928
 
TFG-RARA: A novel fusion gene in acute promyelocytic leukemia that is responsive to all-trans retinoic acid
Chong ML, Cheng H, Xu P, You H, Wang M, Wang L, Ho HH
Leuk Res 2018 Nov;74:51-54
PMID 30292835
 
A non-classical translocation involving 17q12 (retinoic acid receptor alpha) in acute promyelocytic leukemia (APML) with atypical features
Corey SJ, Locker J, Oliveri DR, Shekhter-Levin S, Redner RL, Penchansky L, Gollin SM
Leukemia 1994 Aug;8(8):1350-3
PMID 8057672
 
STAT5B (signal transducer and activator of transcription 5B).
Del Rosario AM, Bernaciak TM, Silva CM.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(2):106-110. http://atlasgeneticsoncology.org//Genes/STAT5BID217ch17q21.html
 
Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor
Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG
Science 2002 Feb 8;295(5557):1079-82
PMID 11834837
 
Essential role for the dimerization domain of NuMA-RARalpha in its oncogenic activities and localization to NuMA sites within the nucleus
Dong S, Qiu J, Stenoien DL, Brinkley WR, Mancini MA, Tweardy DJ
Oncogene 2003 Feb 13;22(6):858-68
PMID 12584566
 
Interactions of STAT5b-RARalpha, a novel acute promyelocytic leukemia fusion protein, with retinoic acid receptor and STAT3 signaling pathways
Dong S, Tweardy DJ
Blood 2002 Apr 15;99(8):2637-46
PMID 11929748
 
Elevation of highly up-regulated in liver cancer (HULC) by hepatitis B virus X protein promotes hepatoma cell proliferation via down-regulating p18
Du Y, Kong G, You X, Zhang S, Zhang T, Gao Y, Ye L, Zhang X
J Biol Chem 2012 Jul 27;287(31):26302-11
PMID 22685290
 
Screening of underlying genetic biomarkers for ankylosing spondylitis
Fan X, Qi B, Ma L, Ma F
Mol Med Rep 2019 Jun;19(6):5263-5274
PMID 31059041
 
Genomic screen for genes involved in mammalian craniofacial development
Fowles LF, Bennetts JS, Berkman JL, Williams E, Koopman P, Teasdale RD, Wicking C
Genesis 2003 Feb;35(2):73-87
PMID 12533789
 
Driver Fusions and Their Implications in the Development and Treatment of Human Cancers
Gao Q, Liang WW, Foltz SM, Mutharasu G, Jayasinghe RG, Cao S, Liao WW, Reynolds SM, Wyczalkowski MA, Yao L, Yu L, Sun SQ; Fusion Analysis Working Group; Cancer Genome Atlas Research Network, Chen K, Lazar AJ, Fields RC, Wendl MC, Van Tine BA, Vij R, Chen F, Nykter M, Shmulevich I, Ding L
Cell Rep 2018 Apr 3;23(1):227-238
PMID 29617662
 
Nucleophosmin and cancer
Grisendi S, Mecucci C, Falini B, Pandolfi PP
Nat Rev Cancer 2006 Jul;6(7):493-505
PMID 16794633
 
Identification of two novel BRCA1-partner genes in the DNA double-strand break repair pathway
Guglielmi C, Cerri I, Evangelista M, Collavoli A, Tancredi M, Aretini P, Caligo MA
Breast Cancer Res Treat 2013 Oct;141(3):515-22
 
Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer
Gurung PM, Veerakumarasivam A, Williamson M, Counsell N, Douglas J, Tan WS, Feber A, Crabb SJ, Short SC, Freeman A, Powles T, Hoskin PJ, West CM, Kelly JD
Int J Cancer 2015 Feb 1;136(3):709-20
PMID 24917520
 
The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers
Hassan MK, Kumar D, Naik M, Dixit M
PLoS One 2018 Jan 17;13(1):e0191377
PMID 29342219
 
Transcriptional-Readthrough RNAs Reflect the Phenomenon of "A Gene Contains Gene(s)" or "Gene(s) within a Gene" in the Human Genome, and Thus Are Not Chimeric RNAs
He Y, Yuan C, Chen L, Lei M, Zellmer L, Huang H, Liao DJ
Genes (Basel) 2018 Jan 16;9(1)
PMID 29337901
 
PML: Regulation and multifaceted function beyond tumor suppression
Hsu KS, Kao HY
Cell Biosci 2018 Jan 25;8:5
 
Role of Pseudogenes in Tumorigenesis
Hu X, Yang L, Mo YY
Cancers (Basel) 2018 Aug 1;10(8)
PMID 30071685
 
t(17;17)(q21;q21), dup(17)(q12q21).
Huret JL.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2):155-156. http://atlasgeneticsoncology.org//Anomalies/t1717q21q21ID1456.html
 
A catalogue of putative HIV-1 protease host cell substrates
Impens F, Timmerman E, Staes A, Moens K, Ariün KK, Verhasselt B, Vandekerckhove J, Gevaert K
Biol Chem 2012 Sep;393(9):915-31
PMID 22944692
 
Effects on human transcriptome of mutated BRCA1 BRCT domain: a microarray study
Iofrida C, Melissari E, Mariotti V, Guglielmi C, Guidugli L, Caligo MA, Pellegrini S
BMC Cancer 2012 May 30;12:207
PMID 22646717
 
Global landscape of HIV-human protein complexes
Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ
Nature 2011 Dec 21;481(7381):365-70
PMID 22190034
 
The cryptic IRF2BP2-RARA fusion transforms hematopoietic stem/progenitor cells and induces retinoid-sensitive acute promyelocytic leukemia
Jovanovic JV, Chillón MC, Vincent-Fabert C, Dillon R, Voisset E, Gutiérrez NC, Sanz RG, Lopez AA, Morgan YG, Lok J, Solomon E, Duprez E, Díaz MG, Grimwade D
Leukemia 2017 Mar;31(3):747-751
PMID 27872498
 
Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML
Kakizuka A, Miller WH Jr, Umesono K, Warrell RP Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM
Cell 1991 Aug 23;66(4):663-74
PMID 1652368
 
AIMP3/p18 controls translational initiation by mediating the delivery of charged initiator tRNA to initiation complex
Kang T, Kwon NH, Lee JY, Park MC, Kang E, Kim HH, Kang TJ, Kim S
J Mol Biol 2012 Nov 2;423(4):475-81
PMID 22867704
 
AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells
Kim SM, Jeon Y, Kim D, Jang H, Bae JS, Park MK, Kim H, Kim S, Lee H
Cell Death Dis 2018 Sep 24;9(10):972
PMID 30250065
 
Expression of AIMP1, 2 and 3, the scaffolds for the multi-tRNA synthetase complex, is downregulated in gastric and colorectal cancer
Kim SS, Hur SY, Kim YR, Yoo NJ, Lee SH
Tumori 2011 May-Jun;97(3):380-5
PMID 21789020
 
The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia
Kondo T, Mori A, Darmanin S, Hashino S, Tanaka J, Asaka M
Haematologica 2008 Sep;93(9):1414-6
PMID 18603554
 
GTF2I-RARA is a novel fusion transcript in a t(7;17) variant of acute promyelocytic leukaemia with clinical resistance to retinoic acid
Li J, Zhong HY, Zhang Y, Xiao L, Bai LH, Liu SF, Zhou GB, Zhang GS
Br J Haematol 2015 Mar;168(6):904-8
PMID 25284716
 
Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17)
Licht JD, Chomienne C, Goy A, Chen A, Scott AA, Head DR, Michaux JL, Wu Y, DeBlasio A, Miller WH Jr, et al
Blood 1995 Feb 15;85(4):1083-94
PMID 7849296
 
Acquisition of oncogenic potential by RAR chimeras in acute promyelocytic leukemia through formation of homodimers
Lin RJ, Evans RM
Mol Cell 2000 May;5(5):821-30
PMID 10882118
 
Concise Review: Balancing Stem Cell Self-Renewal and Differentiation with PLZF
Liu TM, Lee EH, Lim B, Shyh-Chang N
Stem Cells 2016 Feb;34(2):277-87
PMID 26676652
 
Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning
Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z
Proc Natl Acad Sci U S A 1998 Jul 7;95(14):8175-80
PMID 9653160
 
PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia
Martens JH, Brinkman AB, Simmer F, Francoijs KJ, Nebbioso A, Ferrara F, Altucci L, Stunnenberg HG
Cancer Cell 2010 Feb 17;17(2):173-85
PMID 20159609
 
IRF2BP2-RARA t(1;17)(q42
Mazharuddin S, Chattopadhyay A, Levy MY, Redner RL
3;q21 2) APL blasts differentiate in response to all-trans retinoic acid
PMID 29350080
 
Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist
McKeown MR, Corces MR, Eaton ML, Fiore C, Lee E, Lopez JT, Chen MW, Smith D, Chan SM, Koenig JL, Austgen K, Guenther MG, Orlando DA, Lovén J, Fritz CC, Majeti R
Cancer Discov 2017 Oct;7(10):1136-1153
PMID 28729405
 
Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia
Melnick A, Licht JD
Blood 1999 May 15;93(10):3167-215
PMID 10233871
 
A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion
Miller CA, Tricarico C, Skidmore ZL, Uy GL, Lee YS, Hassan A, O'Laughlin MD, Schmidt H, Tian L, Duncavage EJ, Griffith M, Griffith OL, Welch JS, Wartman LD
Blood Adv 2018 Jun 12;2(11):1295-1299
PMID 29891591
 
The Aminoacyl-tRNA Synthetase Complex
Mirande M
Subcell Biochem 2017;83:505-522
PMID 28271488
 
Distinct pattern of gene expression in pyothorax-associated lymphoma (PAL), a lymphoma developing in long-standing inflammation
Nishiu M, Tomita Y, Nakatsuka S, Takakuwa T, Iizuka N, Hoshida Y, Ikeda J, Iuchi K, Yanagawa R, Nakamura Y, Aozasa K
Cancer Sci 2004 Oct;95(10):828-34
PMID 15504251
 
The self-association coiled-coil domain of PML is sufficient for the oncogenic conversion of the retinoic acid receptor (RAR) alpha
Occhionorelli M, Santoro F, Pallavicini I, Gruszka A, Moretti S, Bossi D, Viale A, Shing D, Ronzoni S, Muradore I, Soncini M, Pruneri G, Rafaniello P, Viale G, Pelicci PG, Minucci S
Leukemia 2011 May;25(5):814-20
PMID 21331069
 
Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice
Oh YS, Kim DG, Kim G, Choi EC, Kennedy BK, Suh Y, Park BJ, Kim S
Aging Cell 2010 Oct;9(5):810-22
PMID 20726853
 
Recurrent RARB Translocations in Acute Promyelocytic Leukemia Lacking RARA Translocation
Osumi T, Tsujimoto SI, Tamura M, Uchiyama M, Nakabayashi K, Okamura K, Yoshida M, Tomizawa D, Watanabe A, Takahashi H, Hori T, Yamamoto S, Hamamoto K, Migita M, Ogata-Kawata H, Uchiyama T, Kizawa H, Ueno-Yokohata H, Shirai R, Seki M, Ohki K, Takita J, Inukai T, Ogawa S, Kitamura T, Matsumoto K, Hata K, Kiyokawa N, Goyama S, Kato M
Cancer Res 2018 Aug 15;78(16):4452-4458
PMID 29921692
 
The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR
Park BJ, Kang JW, Lee SW, Choi SJ, Shin YK, Ahn YH, Choi YH, Choi D, Lee KS, Kim S
Cell 2005 Jan 28;120(2):209-21
PMID 15680327
 
AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability
Park BJ, Oh YS, Park SY, Choi SJ, Rudolph C, Schlegelberger B, Kim S
Cancer Res 2006 Jul 15;66(14):6913-8
PMID 16849534
 
What's up and down with histone deacetylation and transcription? Cell
Pazin MJ, Kadonaga JT
1997 May 2;89(3):325-8 Review
PMID 9150131
 
Coordination of eukaryotic translation elongation factor 1A (eEF1A) function in actin organization and translation elongation by the guanine nucleotide exchange factor eEF1Balpha
Pittman YR, Kandl K, Lewis M, Valente L, Kinzy TG
J Biol Chem 2009 Feb 13;284(7):4739-47
PMID 19095653
 
Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}
Qiu JJ, Lu X, Zeisig BB, Ma Z, Cai X, Chen S, Gronemeyer H, Tweardy DJ, So CW, Dong S
Blood 2010 Jan 21;115(3):643-52
PMID 19965660
 
The p18 component of the multisynthetase complex shares a protein motif with the beta and gamma subunits of eukaryotic elongation factor 1
Quevillon S, Mirande M
FEBS Lett 1996 Oct 14;395(1):63-7
PMID 8849690
 
NuMA after 30 years: the matrix revisited
Radulescu AE, Cleveland DW
Trends Cell Biol 2010 Apr;20(4):214-22
PMID 20137953
 
Variations on a theme: the alternate translocations in APL
Redner RL
Leukemia 2002 Oct;16(10):1927-32
PMID 12357344
 
The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion
Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ
Blood 1996 Feb 1;87(3):882-6
PMID 8562957
 
Interaction with RXR is necessary for NPM-RAR-induced myeloid differentiation blockade
Rush EA, Pollock SL, Abecassis I, Redner RL
Leuk Res 2013 Dec;37(12):1704-10
PMID 24183235
 
A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements
Sainty D, Liso V, Cant-Rajnoldi A, Head D, Mozziconacci MJ, Arnoulet C, Benattar L, Fenu S, Mancini M, Duchayne E, Mahon FX, Gutierrez N, Birg F, Biondi A, Grimwade D, Lafage-Pochitaloff M, Hagemeijer A, Flandrin G; Groupe Français d'Hématologie Cellulaire; Groupe Français de Cytogénétique Hématologique; UK Cancer Cytogenetics Group; BIOMED 1 European Community-Concerted Action "Molecular Cytogenetic Diagnosis in Haematological Malignancies"
Blood 2000 Aug 15;96(4):1287-96
PMID 10942370
 
Characterization of p43(ARF), a derivative of the p43 component of multiaminoacyl-tRNA synthetase complex released during apoptosis
Shalak V, Guigou L, Kaminska M, Wautier MP, Wautier JL, Mirande M
J Biol Chem 2007 Apr 13;282(15):10935-43
PMID 17303557
 
New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion
Shimomura Y, Mitsui H, Yamashita Y, Kamae T, Kanai A, Matsui H, Ishibashi T, Tanimura A, Shibayama H, Oritani K, Kuyama J, Kanakura Y
Cancer Sci 2016 Aug;107(8):1165-8
PMID 27193600
 
Epigenetic changes in individuals with arsenicosis
Smeester L, Rager JE, Bailey KA, Guan X, Smith N, García-Vargas G, Del Razo LM, Drobná Z, Kelkar H, Stýblo M, Fry RC
Chem Res Toxicol 2011 Feb 18;24(2):165-7
PMID 21291286
 
Genomic landscapes of breast fibroepithelial tumors
Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM, Rajasegaran V, Myint SS, Nagarajan S, Thangaraju S, Dey S, Nasir ND, Wijaya GC, Lim JQ, Huang D, Li Z, Wong BH, Chan JY, McPherson JR, Cutcutache I, Poore G, Tay ST, Tan WJ, Putti TC, Ahmad BS, Iau P, Chan CW, Tang AP, Yong WS, Madhukumar P, Ho GH, Tan VK, Wong CY, Hartman M, Ong KW, Tan BK, Rozen SG, Tan P, Tan PH, Teh BT
Nat Genet 2015 Nov;47(11):1341-5
PMID 26437033
 
Mapping the contact surfaces in the Lamin A:AIMP3 complex by hydrogen/deuterium exchange FT-ICR mass spectrometry
Tao Y, Fang P, Kim S, Guo M, Young NL, Marshall AG
PLoS One 2017 Aug 10;12(8):e0181869
PMID 28797100
 
Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients
Testa U, Lo-Coco F
Ann Hematol 2016 Apr;95(5):673-80
PMID 26920716
 
Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors
Umesono K, Murakami KK, Thompson CC, Evans RM
Cell 1991 Jun 28;65(7):1255-66
PMID 1648450
 
Histone acetyltransferases in control
Wade PA, Wolffe AP
Curr Biol 1997 Feb 1;7(2):R82-4
PMID 9081669
 
Novel FNDC3B and MECOM fusion and WT1 L378fs* 7 frameshift mutation in an acute myeloid leukaemia patient with cytomorphological and immunophenotypic features reminiscent of acute promyelocytic leukaemia
Wang HY, McMahon C, Ali SM, Young LE, Yekezare S, Ross JS, Ball ED
Br J Haematol 2016 Mar;172(6):987-90
PMID 26147192
 
Acute promyelocytic leukemia: from highly fatal to highly curable
Wang ZY, Chen Z
Blood 2008 Mar 1;111(5):2505-15
PMID 18299451
 
Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia
Wells RA, Catzavelos C, Kamel-Reid S
Nat Genet 1997 Sep;17(1):109-13
PMID 9288109
 
A new variant translocation in acute promyelocytic leukaemia: molecular characterization and clinical correlation
Wells RA, Hummel JL, De Koven A, Zipursky A, Kirby M, Dubé I, Kamel-Reid S
Leukemia 1996 Apr;10(4):735-40
PMID 8618456
 
Involvement of intact HPV16 E6/E7 gene expression in head and neck cancers with unaltered p53 status and perturbed pRb cell cycle control
Wiest T, Schwarz E, Enders C, Flechtenmacher C, Bosch FX
Oncogene 2002 Feb 28;21(10):1510-7
PMID 11896579
 
OBFC2A/RARA: a novel fusion gene in variant acute promyelocytic leukemia
Won D, Shin SY, Park CJ, Jang S, Chi HS, Lee KH, Lee JO, Seo EJ
Blood 2013 Feb 21;121(8):1432-5
PMID 23287866
 
BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia
Yamamoto Y, Tsuzuki S, Tsuzuki M, Handa K, Inaguma Y, Emi N
Blood 2010 Nov 18;116(20):4274-83
PMID 20807888
 
RNF8 is responsible for ATRA resistance in variant acute promyelocytic leukemia with GTF2I/RARA fusion, and inhibition of the ubiquitin-proteasome pathway contributes to the reversion of ATRA resistance
Yan W, Li J, Zhang Y, Yin Y, Cheng Z, Wang J, Hu G, Liu S, Wang Y, Xu Y, Peng H, Zhang G
Cancer Cell Int 2019 Apr 4;19:84
PMID 30992691
 
Molecular Characteristics and Clinical Significance of 12 Fusion Genes in Acute Promyelocytic Leukemia: A Systematic Review
Yan W, Zhang G
Acta Haematol 2016;136(1):1-15
PMID 27089249
 
Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic leukemia
Yin CC, Jain N, Mehrotra M, Zhagn J, Protopopov A, Zuo Z, Pemmaraju N, DiNardo C, Hirsch-Ginsberg C, Wang SA, Medeiros LJ, Chin L, Patel KP, Ravandi F, Futreal A, Bueso-Ramos CE
J Natl Compr Canc Netw 2015 Jan;13(1):19-22
PMID 25583766
 
The landscape and therapeutic relevance of cancer-associated transcript fusions
Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG
Oncogene 2015 Sep 10;34(37):4845-54
PMID 25500544
 
HULC: an oncogenic long non-coding RNA in human cancer
Yu X, Zheng H, Chan MT, Wu WK
J Cell Mol Med 2017 Feb;21(2):410-417
PMID 27781386
 
t(3;17)(q26;q12-21) TBL1XR1/RARA.
Zamecnikova A.
Atlas Genet Cytogenet Oncol Haematol. 2018; 22(4):167-169. http://atlasgeneticsoncology.org//Anomalies/t0317q26q21ID1602.html
 
Clinical characteristics of acute promyelocytic leukemia with the STAT5B-RARA fusion gene
Zhang C, Wang Y, Liu B, Gong B, Gong X, Liu Y, Mi Y, Wang J
Blood Cells Mol Dis 2018 Mar;69:71-73
PMID 29030091
 
The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR
de Thé H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A
Cell 1991 Aug 23;66(4):675-84
PMID 1652369
 

Citation

This paper should be referenced as such :
Viguié F
RARA (Retinoic acid receptor, alpha);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/RARAID46.html
History of this paper:
Viguié, F. RARA (retinoic acid receptor, alpha). Atlas Genet Cytogenet Oncol Haematol. 2000;4(4):195-196.
http://documents.irevues.inist.fr/bitstream/handle/2042/37670/10-2000-RARAID46.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias M3ANLLID1240 t0117p34q21ID1603 t0217q32q21ID1601 t0317q26q21ID1602 t0417q12q21ID1470
t0717q11q21ID1711 t0X17p11q21ID1594 t1117ID1028 t1117ID1126 t1117ID1179
t1517ID1035 t1717q21q21ID1456 t1717q21q24ID1497 t517ID1081 TL_ins1517q22q21q21ID3101
TL_ins1517q22q21q26ID3100 TL_t1217p13q21ID1694


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 21 ]

Solid Tumors TT_t0417p16q21ID106275 TT_t0617q22q21ID106973 TT_t0817q21q21ID107931 TT_t1117q13q21ID100982 TT_t1117q14q21ID100997
TT_t1717q11q21ID102454 TT_t1717q11q21ID102455 TT_t1717q11q21ID102457 TT_t1717q12q21ID102520 TT_t1717q12q21ID102521
TT_t1717q12q21ID102522 TT_t1717q21q21ID102593 TT_t1717q21q21ID102594 TT_t1717q21q21ID102595 TT_t1717q21q21ID102596
TT_t1717q21q21ID102597 TT_t1717q21q21ID102598 TT_t1717q21q21ID102599 TT_t1717q21q22ID102632 TT_t1717q21q22ID102633
TT_t1717q21q22ID102634


External links

Nomenclature
HGNC (Hugo)RARA   9864
LRG (Locus Reference Genomic)LRG_1070
Cards
AtlasRARAID46
Entrez_Gene (NCBI)RARA  5914  retinoic acid receptor alpha
AliasesNR1B1; RAR
GeneCards (Weizmann)RARA
Ensembl hg19 (Hinxton)ENSG00000131759 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000131759 [Gene_View]  ENSG00000131759 [Sequence]  chr17:40318221-40357643 [Contig_View]  RARA [Vega]
ICGC DataPortalENSG00000131759
TCGA cBioPortalRARA
AceView (NCBI)RARA
Genatlas (Paris)RARA
WikiGenes5914
SOURCE (Princeton)RARA
Genetics Home Reference (NIH)RARA
Genomic and cartography
GoldenPath hg38 (UCSC)RARA  -     chr17:40318221-40357643 +  17q21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RARA  -     17q21.2   [Description]    (hg19-Feb_2009)
GoldenPathRARA - 17q21.2 [CytoView hg19]  RARA - 17q21.2 [CytoView hg38]
ImmunoBaseENSG00000131759
Mapping of homologs : NCBIRARA [Mapview hg19]  RARA [Mapview hg38]
OMIM180240   612376   
Gene and transcription
Genbank (Entrez)AK098172 AK130192 AK292205 AK303868 AK312564
RefSeq transcript (Entrez)NM_000964 NM_001024809 NM_001033603 NM_001145301 NM_001145302
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RARA
Alternative Splicing GalleryENSG00000131759
Gene ExpressionRARA [ NCBI-GEO ]   RARA [ EBI - ARRAY_EXPRESS ]   RARA [ SEEK ]   RARA [ MEM ]
Gene Expression Viewer (FireBrowse)RARA [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5914
GTEX Portal (Tissue expression)RARA
Human Protein AtlasENSG00000131759-RARA [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP10276   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP10276  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP10276
Splice isoforms : SwissVarP10276
PhosPhoSitePlusP10276
Domaine pattern : Prosite (Expaxy)NR_LBD (PS51843)    NUCLEAR_REC_DBD_1 (PS00031)    NUCLEAR_REC_DBD_2 (PS51030)   
Domains : Interpro (EBI)NHR-like_dom_sf    Nucl_hrmn_rcpt_lig-bd    Nuclear_hrmn_rcpt    Retinoic_acid_rcpt    Znf_hrmn_rcpt    Znf_NHR/GATA   
Domain families : Pfam (Sanger)Hormone_recep (PF00104)    zf-C4 (PF00105)   
Domain families : Pfam (NCBI)pfam00104    pfam00105   
Domain families : Smart (EMBL)HOLI (SM00430)  ZnF_C4 (SM00399)  
Conserved Domain (NCBI)RARA
DMDM Disease mutations5914
Blocks (Seattle)RARA
PDB (RSDB)1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
PDB Europe1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
PDB (PDBSum)1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
PDB (IMB)1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
Structural Biology KnowledgeBase1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
SCOP (Structural Classification of Proteins)1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
CATH (Classification of proteins structures)1DKF    1DSZ    3A9E    3KMR    3KMZ    4DQM    5K13   
SuperfamilyP10276
Human Protein Atlas [tissue]ENSG00000131759-RARA [tissue]
Peptide AtlasP10276
HPRD06769
IPIIPI00020071   IPI00218375   IPI00908598   IPI00470378   IPI00922641   IPI00014923   IPI00791851   
Protein Interaction databases
DIP (DOE-UCLA)P10276
IntAct (EBI)P10276
FunCoupENSG00000131759
BioGRIDRARA
STRING (EMBL)RARA
ZODIACRARA
Ontologies - Pathways
QuickGOP10276
Ontology : AmiGOnegative regulation of transcription by RNA polymerase II  nuclear chromatin  nuclear chromatin  translation repressor activity, mRNA regulatory element binding  transcription regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  ureteric bud development  neural tube closure  liver development  retinoic acid binding  glandular epithelial cell development  outflow tract septum morphogenesis  growth plate cartilage development  DNA-binding transcription factor activity  steroid hormone receptor activity  transcription coactivator activity  transcription coactivator activity  transcription corepressor activity  nuclear receptor activity  signaling receptor binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  transcription initiation from RNA polymerase II promoter  protein phosphorylation  signal transduction  multicellular organism development  germ cell development  spermatogenesis  female pregnancy  transcription factor binding  transcription factor binding  drug binding  zinc ion binding  positive regulation of cell proliferation  negative regulation of cell proliferation  hormone-mediated signaling pathway  cell surface  actin cytoskeleton  negative regulation of translation  enzyme binding  protein domain specific binding  hippocampus development  cell differentiation  nuclear receptor transcription coactivator activity  dendrite  prostate gland development  negative regulation of granulocyte differentiation  embryonic camera-type eye development  chromatin DNA binding  regulation of myelination  response to estradiol  response to retinoic acid  response to retinoic acid  negative regulation of interferon-gamma production  negative regulation of tumor necrosis factor production  positive regulation of interleukin-13 production  positive regulation of interleukin-4 production  positive regulation of interleukin-5 production  response to vitamin A  response to lipid  response to cytokine  multicellular organism growth  signaling receptor activity  signaling receptor activity  histone deacetylase binding  negative regulation of apoptotic process  apoptotic cell clearance  steroid hormone mediated signaling pathway  protein kinase B binding  retinoic acid-responsive element binding  response to ethanol  positive regulation of T-helper 2 cell differentiation  positive regulation of neuron differentiation  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  protein heterodimerization activity  mRNA 5'-UTR binding  regulation of synaptic plasticity  retinoic acid receptor signaling pathway  retinoic acid receptor signaling pathway  perinuclear region of cytoplasm  gland development  protein kinase A binding  positive regulation of binding  alpha-actinin binding  ventricular cardiac muscle cell differentiation  Sertoli cell fate commitment  limb development  face development  bone morphogenesis  epithelium development  trachea cartilage development  chondroblast differentiation  negative regulation of cartilage development  cellular response to lipopolysaccharide  cellular response to retinoic acid  cellular response to retinoic acid  cellular response to estrogen stimulus  RNA polymerase II transcription factor complex  
Ontology : EGO-EBInegative regulation of transcription by RNA polymerase II  nuclear chromatin  nuclear chromatin  translation repressor activity, mRNA regulatory element binding  transcription regulatory region sequence-specific DNA binding  RNA polymerase II regulatory region sequence-specific DNA binding  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription factor activity, RNA polymerase II-specific  ureteric bud development  neural tube closure  liver development  retinoic acid binding  glandular epithelial cell development  outflow tract septum morphogenesis  growth plate cartilage development  DNA-binding transcription factor activity  steroid hormone receptor activity  transcription coactivator activity  transcription coactivator activity  transcription corepressor activity  nuclear receptor activity  signaling receptor binding  protein binding  nucleus  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  transcription initiation from RNA polymerase II promoter  protein phosphorylation  signal transduction  multicellular organism development  germ cell development  spermatogenesis  female pregnancy  transcription factor binding  transcription factor binding  drug binding  zinc ion binding  positive regulation of cell proliferation  negative regulation of cell proliferation  hormone-mediated signaling pathway  cell surface  actin cytoskeleton  negative regulation of translation  enzyme binding  protein domain specific binding  hippocampus development  cell differentiation  nuclear receptor transcription coactivator activity  dendrite  prostate gland development  negative regulation of granulocyte differentiation  embryonic camera-type eye development  chromatin DNA binding  regulation of myelination  response to estradiol  response to retinoic acid  response to retinoic acid  negative regulation of interferon-gamma production  negative regulation of tumor necrosis factor production  positive regulation of interleukin-13 production  positive regulation of interleukin-4 production  positive regulation of interleukin-5 production  response to vitamin A  response to lipid  response to cytokine  multicellular organism growth  signaling receptor activity  signaling receptor activity  histone deacetylase binding  negative regulation of apoptotic process  apoptotic cell clearance  steroid hormone mediated signaling pathway  protein kinase B binding  retinoic acid-responsive element binding  response to ethanol  positive regulation of T-helper 2 cell differentiation  positive regulation of neuron differentiation  positive regulation of cell cycle  negative regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription, DNA-templated  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  positive regulation of transcription by RNA polymerase II  protein heterodimerization activity  mRNA 5'-UTR binding  regulation of synaptic plasticity  retinoic acid receptor signaling pathway  retinoic acid receptor signaling pathway  perinuclear region of cytoplasm  gland development  protein kinase A binding  positive regulation of binding  alpha-actinin binding  ventricular cardiac muscle cell differentiation  Sertoli cell fate commitment  limb development  face development  bone morphogenesis  epithelium development  trachea cartilage development  chondroblast differentiation  negative regulation of cartilage development  cellular response to lipopolysaccharide  cellular response to retinoic acid  cellular response to retinoic acid  cellular response to estrogen stimulus  RNA polymerase II transcription factor complex  
Pathways : KEGGPathways in cancer    Transcriptional misregulation in cancer    Acute myeloid leukemia   
REACTOMEP10276 [protein]
REACTOME PathwaysR-HSA-5617472 [pathway]   
NDEx NetworkRARA
Atlas of Cancer Signalling NetworkRARA
Wikipedia pathwaysRARA
Orthology - Evolution
OrthoDB5914
GeneTree (enSembl)ENSG00000131759
Phylogenetic Trees/Animal Genes : TreeFamRARA
HOGENOMP10276
Homologs : HomoloGeneRARA
Homology/Alignments : Family Browser (UCSC)RARA
Gene fusions - Rearrangements
Fusion : Mitelman-/17q21.2 [RARA/ins(15;17)(q22;q21q21)|ins(15;17)(q22;q21q26)]  
Fusion : MitelmanBCOR/RARA [Xp11.4/17q21.2]  [t(X;17)(p11;q21)]  
Fusion : MitelmanFIP1L1/RARA [4q12/17q21.2]  [t(4;17)(q12;q21)]  
Fusion : MitelmanGTF2I/RARA [7q11.23/17q21.2]  [t(7;17)(q11;q21)]  
Fusion : MitelmanNABP1/RARA [2q32.3/17q21.2]  [t(2;17)(q32;q21)]  
Fusion : MitelmanNPM1/RARA [5q35.1/17q21.2]  [t(11;17)(q23;q21)]  [t(15;17)(q22;q21)]  
[t(5;17)(q35;q21)]  
Fusion : MitelmanNUMA1/RARA [11q13.4/17q21.2]  [t(11;17)(q13;q21)]  
Fusion : MitelmanPML/RARA [15q24.1/17q21.2]  [ins(15;17)(q22;q21q21)]  [ins(17;15)(q21;q22q22)]  
[ins(4;15)(q21;q?q22)t(15;17)(q22;q21)]  [t(11;17)(q23;q21)]  [t(11;17;15)(q13;q21;q22)]  
[t(13;17;15)(p13;q21;q22)]  [t(15;17)(q22;q21)]  [t(15;17;16)(q22;q21;q13)]  [t(15;17;18)(q22;q21;q12)]  
[t(15;17;19)(q22;q21;q13)]  [t(1;17;15)(p32;q21;q22)]  [t(3;17;15)(p21;q21;q22)]  [t(3;17;15)(q27;q21;q22)]  
[t(5;17)(q35;q21)]  [t(5;17;15)(q11;q21;q22)]  [t(5;17;15)(q14;q21;q22)]  [t(5;17;15)(q35;q21;q22)]  
[t(6;17;15)(p21;q21;q22)]  [t(7;17;15)(q22;q21;q22)]  [t(8;17;15)(q22;q21;q22)]  [t(8;17;15)(q24;q21;q22)]  
[t(9;17;15)(q31;q21;q22)]  
Fusion : MitelmanPRKAR1A/RARA [17q24.2/17q21.2]  [t(17;17)(q21;q24)]  
Fusion : MitelmanRARA/CA10 [17q21.2/17q21.33]  [t(17;17)(q21;q22)]  
Fusion : MitelmanRARA/CDC6 [17q21.2/17q21.2]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/CDK12 [17q21.2/17q12]  [t(17;17)(q12;q21)]  
Fusion : MitelmanRARA/COL10A1 [17q21.2/6q22.1]  [t(6;17)(q22;q21)]  
Fusion : MitelmanRARA/HOXB3 [17q21.2/17q21.32]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/MSL1 [17q21.2/17q21.1]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/MYO1D [17q21.2/17q11.2]  [t(17;17)(q11;q21)]  
Fusion : MitelmanRARA/NARS2 [17q21.2/11q14.1]  [t(11;17)(q14;q21)]  
Fusion : MitelmanRARA/PCTP [17q21.2/17q22]  [t(17;17)(q21;q22)]  
Fusion : MitelmanRARA/PGAP3 [17q21.2/17q12]  [t(17;17)(q12;q21)]  
Fusion : MitelmanRARA/PKIA [17q21.2/8q21.12]  [t(8;17)(q21;q21)]  
Fusion : MitelmanRARA/PML [17q21.2/15q24.1]  [t(15;17)(q22;q21)]  
Fusion : MitelmanRARA/POLDIP2 [17q21.2/17q11.2]  [t(17;17)(q11;q21)]  
Fusion : MitelmanRARA/PRR11 [17q21.2/17q22]  [t(17;17)(q21;q22)]  
Fusion : MitelmanRARA/PSMD3 [17q21.2/17q21.1]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/SKAP1 [17q21.2/17q21.32]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/STAC2 [17q21.2/17q12]  [t(17;17)(q12;q21)]  
Fusion : MitelmanRARA/STAT3 [17q21.2/17q21.2]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/WIPF2 [17q21.2/17q21.1]  [t(17;17)(q21;q21)]  
Fusion : MitelmanRARA/ZNF595 [17q21.2/4p16.3]  [t(4;17)(p16;q21)]  
Fusion : MitelmanSTAT5B/RARA [17q21.2/17q21.2]  [t(17;17)(q21;q21)]  
Fusion : MitelmanTAOK1/RARA [17q11.2/17q21.2]  [t(17;17)(q11;q21)]  
Fusion : MitelmanTBL1XR1/RARA [3q26.32/17q21.2]  [t(3;17)(q26;q21)]  
Fusion : MitelmanTPCN2/RARA [11q13.3/17q21.2]  [t(11;17)(q13;q21)]  
Fusion : MitelmanZBTB16/RARA [11q23.2/17q21.2]  [ins(11;17)(q23;q21q21)]  [t(11;17)(q23;q21)]  
[t(15;17)(q22;q21)]  [t(5;17)(q35;q21)]  
Fusion : COSMICPML [15q24.1]  -  RARA [17q21.2]  [fusion_2299]  [fusion_2300]  [fusion_2301]  [fusion_2302]  [fusion_2304]  [fusion_2305]  [fusion_2307]  
[fusion_2310]  [fusion_2312]  [fusion_2313]  [fusion_2316]  [fusion_2317]  [fusion_2318]  [fusion_2320]  [fusion_2322]  
Fusion PortalPML 15q24.1 RARA 17q21.2 LAML
Fusion PortalRARA 17q21.2 CA10 17q21.33 BRCA
Fusion PortalRARA 17q21.2 CDC6 17q21.2 LUAD
Fusion PortalRARA 17q21.2 CDK12 17q12 BRCA
Fusion PortalRARA 17q21.2 COL10A1 6q22.1 BRCA
Fusion PortalRARA 17q21.2 HOXB3 17q21.32 BRCA
Fusion PortalRARA 17q21.2 MSL1 17q21.1 BRCA
Fusion PortalRARA 17q21.2 MYO1D 17q11.2 BRCA
Fusion PortalRARA 17q21.2 PCTP 17q22 BRCA
Fusion PortalRARA 17q21.2 PGAP3 17q12 BRCA
Fusion PortalRARA 17q21.2 PML 15q24.1 LAML
Fusion PortalRARA 17q21.2 PRR11 17q22 BRCA
Fusion PortalRARA 17q21.2 PSMD3 17q21.1 BRCA
Fusion PortalRARA 17q21.2 RP11-1407O15.2 BRCA
Fusion PortalRARA 17q21.2 SKAP1 17q21.32 BRCA
Fusion PortalRARA 17q21.2 STAC2 17q12 LUAD
Fusion PortalRARA 17q21.2 STAT3 17q21.2 BRCA
Fusion PortalRARA 17q21.2 WIPF2 17q21.1 BRCA
Fusion PortalRARA 17q21.2 ZNF595 4p16.3 BRCA
Fusion PortalTAOK1 17q11.2 RARA 17q21.2 GBM
Fusion PortalTPCN2 11q13.3 RARA 17q21.2 BRCA
Fusion : TICdbBCOR [Xp11.4]  -  RARA [17q21.2]
Fusion : TICdbFIP1L1 [4q12]  -  RARA [17q21.2]
Fusion : TICdbNABP1 [2q32.3]  -  RARA [17q21.2]
Fusion : TICdbNPM1 [5q35.1]  -  RARA [17q21.2]
Fusion : TICdbNUMA1 [11q13.4]  -  RARA [17q21.2]
Fusion : TICdbPML [15q24.1]  -  RARA [17q21.2]
Fusion : TICdbPRKAR1A [17q24.2]  -  RARA [17q21.2]
Fusion : TICdbSTAT5B [17q21.2]  -  RARA [17q21.2]
Fusion : TICdbZBTB16 [11q23.2]  -  RARA [17q21.2]
Fusion : FusionGDB15771    22862    23109    24740    25155    27793    28695    30460    30461    30462    30463    30464    30465    30466    30467   
30468    30469    30470    30471    30472    30473    30474    30475    30476    30477    30478    30479    30480    30481    30482   
30483    30484    30485    30486    30487    30488    31596    320    33554    34849    35759    37225    39186    4079    42525   
6729   
Fusion : Fusion_HubACACA--RARA    ACSS1--RARA    AGPAT3--RARA    ALK--RARA    BCAS3--RARA    BCL6--RARA    BCOR--RARA    BPTF--RARA    BRD4--RARA    CASC3--RARA    CCDC170--RARA    CELF2--RARA    CTD-3088G3.8--RARA    CXCR4--RARA    ERBB2--RARA   
FBXL20--RARA    FIP1L1--RARA    FNDC3B--RARA    GOLGA4--RARA    GPR160--RARA    GTF2I--RARA    H2AFV--RARA    HOXB3--RARA    HOXB6--RARA    IKZF3--RARA    IRF2BP2--RARA    KDM6B--RARA    KMT2A--RARA    KRT14--RARA    MCL1--RARA   
MED1--RARA    MED24--RARA    MLL--RARA    MYH10--RARA    MYO1D--RARA    NABP1--RARA    NARS2--RARA    NHP2L1--RARA    NPM1--RARA    NUMA1--RARA    OBFC2A--RARA    PCTP--RARA    PGAP3--RARA    PITPNC1--RARA    PKIA--RARA   
PLA2G4D--RARA    PLXDC1--RARA    PLZF--RARA    PML--RARA    POLDIP2--RARA    PPFIA1--RARA    PRKAR1A--RARA    PRR11--RARA    RAB6A--RARA    RARA--41526    RARA--AC015821.1    RARA--ANKFN1    RARA--ATAD3A    RARA--B2M    RARA--BASP1   
RARA--BCOR    RARA--BRD4    RARA--C16ORF45    RARA--C17ORF108    RARA--C17ORF62    RARA--CA10    RARA--CDC6    RARA--CDK12    RARA--CERS4    RARA--COL10A1    RARA--DPP9    RARA--EIF2B5    RARA--FIP1L1    RARA--FLNA    RARA--GNAS   
RARA--GTF2I    RARA--HMGB1    RARA--HOXB3    RARA--IRF2BP2    RARA--ITGAX    RARA--KIAA0195    RARA--LGALS16    RARA--LIFR    RARA--LTBP1    RARA--METRNL    RARA--MFSD10    RARA--MPO    RARA--MRC2    RARA--MSL1    RARA--MYL   
RARA--MYO1D    RARA--NARS2    RARA--NPM    RARA--NPM1    RARA--NUMA    RARA--NUMA1    RARA--OBFC2A    RARA--PCTP    RARA--PGAP3    RARA--PHRF1    RARA--PKIA    RARA--PL    RARA--PLZF    RARA--PMI    RARA--PML   
RARA--PPP1R13B    RARA--PRKAR1A    RARA--PRR11    RARA--PSMD3    RARA--PTMS    RARA--RARA    RARA--RASSF3    RARA--RBM4    RARA--RCN1    RARA--RP11-1407O15.2    RARA--SAE1    RARA--SKA2    RARA--SKAP1    RARA--SLC9A3R1    RARA--STAC2   
RARA--STAT3    RARA--STAT5B    RARA--STXBP1    RARA--TBLR1    RARA--TIF1    RARA--TRIM24    RARA--TSPYL4    RARA--UBTF    RARA--USP22    RARA--USP32    RARA--VPS13B    RARA--WIPF2    RARA--ZBTB16    RARA--ZNF145    RARA--ZNF276   
RARA--ZNF595    RARA--ZNF718    RARA--ZNF732    RNF43--RARA    RXRA--RARA    SMARCE1--RARA    SMS--RARA    SPOP--RARA    STAT3--RARA    STAT5B--RARA    TAOK1--RARA    TBLR1--RARA    TCFL5--RARA    TPCN2--RARA    WDR59--RARA   
ZBTB16--RARA   
Fusion : QuiverRARA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRARA [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RARA
dbVarRARA
ClinVarRARA
1000_GenomesRARA 
Exome Variant ServerRARA
ExAC (Exome Aggregation Consortium)ENSG00000131759
GNOMAD BrowserENSG00000131759
Varsome BrowserRARA
Genetic variants : HAPMAP5914
Genomic Variants (DGV)RARA [DGVbeta]
DECIPHERRARA [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRARA 
Mutations
ICGC Data PortalRARA 
TCGA Data PortalRARA 
Broad Tumor PortalRARA
OASIS PortalRARA [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRARA  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DRARA
Mutations and Diseases : HGMDRARA
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RARA
DgiDB (Drug Gene Interaction Database)RARA
DoCM (Curated mutations)RARA (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RARA (select a term)
intoGenRARA
NCG5 (London)RARA
Cancer3DRARA(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM180240    612376   
Orphanet8559   
DisGeNETRARA
MedgenRARA
Genetic Testing Registry RARA
NextProtP10276 [Medical]
TSGene5914
GENETestsRARA
Target ValidationRARA
Huge Navigator RARA [HugePedia]
snp3D : Map Gene to Disease5914
BioCentury BCIQRARA
ClinGenRARA
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5914
Chemical/Pharm GKB GenePA34225
Clinical trialRARA
Miscellaneous
canSAR (ICR)RARA (select the gene name)
HarmonizomeRARA
DataMed IndexRARA
Probes
Litterature
PubMed418 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineRARA
EVEXRARA
GoPubMedRARA
iHOPRARA
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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