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t(1;3)(p36;q21) RPN1/PRDM16

Written2016-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean-loup.huret@chu-poitiers.fr

Abstract Review on t(1;3)(p36;q21) translocations, with data on clinics, and the genes involved.

Keywords chromosome 1; chromosome3; t(1;3)(p36;q21); RPN1; PRDM16

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9920/3 Therapy-related myeloid neoplasms
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9873/3 AML without maturation
ICD-Morpho 9874/3 AML with maturation
ICD-Morpho 9867/3 Acute myelomonocytic leukaemia
ICD-Morpho 9891/3 Acute monoblastic and monocytic leukaemia
ICD-Morpho 9840/3 Acute erythroid leukaemia
ICD-Morpho 9983/3 Refractory anaemia with excess blasts
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
ICD-Morpho 9982/3 Refractory anemia with ring sideroblasts associated with marked thrombocytosis; Refractory anaemia with ring sideroblasts
ICD-Morpho 9945/3 Chronic myelomonocytic leukaemia
Atlas_Id 2048
Note A translocation t(1;3)(p36;q21), with the same breakpoints but involving PSMD2 and PRDM16 probably does not exist:
1- PSMD2 sits in 3q27, while the breakpoint is in 3q21;
2- PSMD2, a protein of the proteasome, is mainly known in PubMed by its alias: "RPN1", while the true RPN1, a protein involved in N-glycosylation and sitting in 3q21, is better known by its full name: "Ribophorin I".
Hence the confusion, found in a number of papers of the literature.

Clinics and Pathology

Disease Myelodysplastic syndromes and acute myeloid leukaemias
Note A t(1;3)(p36;q21) RPN1/PRDM16 was found in 35 cases (Mochizuki et al., 2000; Shimizu et al., 2000: Xinh et al., 2003; Duhoux et al., 2012)
Phenotype / cell stem origin There were 19 myeloproliferative/myelodysplastic syndromes: 1 chronic myeloid leukemia (CML), 3 refractory anaemia with ring sideroblasts (RARS); 6 refractory anemia with excess blasts (RAEB, RAEB2, RAEB-T), 6 chronic myelomonocytic leukaemia (CMML) and 3 myelodysplastic syndrome not otherwise specified (MDS-NOS); and 16, acute myeloid leukaemias; 7 apparently de novo (AML- M1, M2, M4, M5a, M6 and NOS), and 9 therapy-related or secondary AML.
Clinics Median age was 66 years (range 29-92). Sex ratio was 21 male/14 female patients (3/5 male, 2/5 female).
 
Survival in 29 patients with t(1;3)(p36;q21) RPN1/PRDM16
Prognosis Median survival in 29 patients was 13-15 months; five patients died within a month after diagnosis, while 2 patients were long survivors (65 months + and 80 months+).

Cytogenetics

Cytogenetics Morphological The t(1;3)(p36;q21) was the sole abnormality in 26 of 35 cases, and accompanied with del(5q) at diagnosis in 5 cases. In 2 additional cases, the del(5q) occurred during course of the disease. There was one del(13q) and one del(20q), markers and a complex karyotype were found in two cases.

Genes involved and Proteins

Gene Name PRDM16
Location 1p36
Dna / Rna 11 splice variants
Protein 1276 amino acids and smaller proteins. Contains a N-term PR domain; 7 Zinc fingers, a proline-rich domain, and 3 Zinc fingers in the C-term. Binds DNA. Transcription activator; PRDM16 has an intrinsic histone methyltransferase activity. PRDM16 forms a transcriptional complex with CEBPB. PRDM16 plays a downstream regulatory role in mediating TGFB signaling (Bjork et al., 2010). PRDM16 induces brown fat determination and differentiation. PRDM16 is expressed selectively in the earliest stem and progenitor hematopoietic cells, and is required for the maintenance of the hematopoietic stem cell pool during development. PRDM16 is also required for survival, cell-cycle regulation and self-renewal in neural stem cells (Chuikov et al., 2010; Kajimura et al., 2010; Aguilo et al., 2011; Chi and Cohen, 2016).
Gene Name RPN1
Location 3q21
Note RPN1 (Ribophorin I) (3q21.3, starts at 128338813 and ends at 128369719 bp from pter) must not be confused with PSMD2 (proteasome 26S subunit, non-ATPase 2) (3q27.1; starts at 184018369 and ends at 184026842 bp from pter). PSMD2 aliases are: RPN1, P97, S2, TRAP2 (see above).
Dna / Rna 8 splice variants
Protein 607 amino acids. RPN1 comprised of a signal peptide (aa 1-23).RPN1 (Ribophorin I) is an endoplasmic reticulum transmembrane protein and a subunit of the oligosaccharyltransferase (OST) complex. RPN1 regulates the delivery of precursor proteins to the OST complex by presenting them to the catalytic core. RPN1 acts as a substrate-specific facilitator of N-glycosylation It may function as a chaperone that recognizes misfolded proteins, and plays a role in protein quality control in association with MLEC (malectin) (Wilson and High, 2007; Wilson et al., 2008; Takeda et al., 2014).

Result of the chromosomal anomaly

Hybrid gene
Description 5' RPN1 translocated to 3' PRDM16. The breakpoint in PRDM16 is located either in the ?rst intron, or 5' of exon 1. Transcriptional activation of can occur in some patients, and fusion transcripts have been generated in other patients.
  
Fusion Protein
Oncogenesis The 5' flanking regions of the rat RPN1 gene containes GC-rich elements and an octamer motif. It could serve as an enhancer, to activate transcription of PRDM16 (Mochizuki et al., 2000; Shimizu et al., 2000). Overexpression of PRDM16 (Duhoux et al., 2012).
  

Bibliography

Prdm16 is a physiologic regulator of hematopoietic stem cells.
Aguilo F, Avagyan S, Labar A, Sevilla A, Lee DF, Kumar P, Lemischka IR, Zhou BY, Snoeck HW.
Blood. 2011 May 12;117(19):5057-66. doi: 10.1182/blood-2010-08-300145. Epub 2011 Feb 22.
PMID 21343612
 
Prdm16 is required for normal palatogenesis in mice.
Bjork BC, Turbe-Doan A, Prysak M, Herron BJ, Beier DR.
Hum Mol Genet. 2010 Mar 1;19(5):774-89. doi: 10.1093/hmg/ddp543. Epub 2009 Dec 11.
PMID 20007998
 
The Multifaceted Roles of PRDM16: Adipose Biology and Beyond.
Chi J, Cohen P.
Trends Endocrinol Metab. 2016 Jan;27(1):11-23. doi: 10.1016/j.tem.2015.11.005. Epub 2015 Dec 11. Review.
PMID 26688472
 
Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.
Chuikov S, Levi BP, Smith ML, Morrison SJ.
Nat Cell Biol. 2010 Oct;12(10):999-1006. doi: 10.1038/ncb2101. Epub 2010 Sep 12.
PMID 20835244
 
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Duhoux FP, Ameye G, Montano-Almendras CP, Bahloula K, Mozziconacci MJ, Laibe S, Wlodarska I, Michaux L, Talmant P, Richebourg S, Lippert E, Speleman F, Herens C, Struski S, Raynaud S, Auger N, Nadal N, Rack K, Mugneret F, Tigaud I, Lafage M, Taviaux S, Roche-Lestienne C, Latinne D, Libouton JM, Demoulin JB, Poirel HA; Groupe Francophone de Cytogénétique Hématologique (GFCH); Belgian Cytogenetic Group for Haematology and Oncology (BCG-HO).
Br J Haematol. 2012 Jan;156(1):76-88. doi: 10.1111/j.1365-2141.2011.08918.x. Epub 2011 Nov 3.
PMID 22050763
 
Initiation of myoblast to brown fat switch by a PRDM16-C/EBP-beta transcriptional complex.
Kajimura S, Seale P, Kubota K, Lunsford E, Frangioni JV, Gygi SP, Spiegelman BM.
Nature. 2009 Aug 27;460(7259):1154-8. Epub 2009 Jul 29.
PMID 19641492
 
A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells.
Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K.
Blood. 2000 Nov 1;96(9):3209-14.
PMID 11050005
 
Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).
Shimizu S, Suzukawa K, Kodera T, Nagasawa T, Abe T, Taniwaki M, Yagasaki F, Tanaka H, Fujisawa S, Johansson B, Ahlgren T, Yokota J, Morishita K.
Genes Chromosomes Cancer. 2000 Mar;27(3):229-38.
PMID 10679911
 
Association of malectin with ribophorin I is crucial for attenuation of misfolded glycoprotein secretion.
Takeda K, Qin SY, Matsumoto N, Yamamoto K.
Biochem Biophys Res Commun. 2014 Nov 21;454(3):436-40. doi: 10.1016/j.bbrc.2014.10.102. Epub 2014 Oct 27.
PMID 25451265
 
Ribophorin I acts as a substrate-specific facilitator of N-glycosylation.
Wilson CM, High S.
J Cell Sci. 2007 Feb 15;120(Pt 4):648-57. Epub 2007 Jan 30.
PMID 17264154
 
Ribophorin I regulates substrate delivery to the oligosaccharyltransferase core.
Wilson CM, Roebuck Q, High S.
Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9534-9. doi: 10.1073/pnas.0711846105. Epub 2008 Jul 7.
PMID 18607003
 
Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.
Xinh PT, Tri NK, Nagao H, Nakazato H, Taketazu F, Fujisawa S, Yagasaki F, Chen YZ, Hayashi Y, Toyoda A, Hattori M, Sakaki Y, Tokunaga K, Sato Y.
Genes Chromosomes Cancer. 2003 Mar;36(3):313-6.
PMID 12557231
 

Citation

This paper should be referenced as such :
Huret JL
t(1;3)(p36;q21) RPN1/PRDM16;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0103p36q21ID2048.html


Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]

Genes TRA TRB TRD

Translocations implicated (Data extracted from papers in the Atlas)

 t(1;3)(p36;q21) RPN1/PRDM16

External links

Mitelman databaset(1;3)(p36;q21) [Case List]    t(1;3)(p36;q21) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9920/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9873/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9874/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9867/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9891/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9840/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9983/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9982/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9945/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(1;3)(p36;q21) RPN1/PRDM16
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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indexed on : Fri Jan 27 12:50:16 CET 2017


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