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t(X;17)(p11;q21) BCOR/RARA

Written2012-01Yukiya Yamamoto
Department of Hematology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1594
 
  t(X;17)(p11;q12), G-banding.

Clinics and Pathology

Disease A variant case of acute promyelocytic leukemia
Epidemiology Very rare. One case has been reported.
Clinics A bone marrow sample was markedly hypercellular, containing 83% promyelocytes. Coagulopathy was present with an increased prothrombin time, an activated partial thromboplastin time, decreased fibrinogen, and mildly increased fibrin/fibrinogen degradation products.
Cytology Bone marrow promyelocytes were strongly positive for Sudan black B, myeloperoxidase staining and naphthol AS-D chloroacetate staining and negative for alpha-naphthyl butyrate staining. Flow cytometric analysis: HLA-DR-/CD13+/CD33+/CD56+.
 
Rectangular cytoplasmic bodies and round inclusions are found in some of hypergranular promyelocytes. May-Giemsa staining.
Treatment Conventional chemotherapy plus ATRA achieved complete remission, followed with consolidation therapies. However, 35 months after diagnosis, the patient relapsed and cord blood transplantation was performed with a myeloablative conditioning regimen. After engraftment was achieved, a bone marrow sample showed third CR. The patient demonstrated overt coagulopathy, sensitivity to ATRA, but resistance to arsenic trioxide.

Cytogenetics

 
  FISH analysis (Vysis LSI PML/RARA dual color, dual fusion translocation probe, Vysis; Downers Grove, IL). One of the RARA signals (green) is split. PML signals (red) are intact.

Genes involved and Proteins

Gene Name BCOR
Location Xp11.4
Protein The BCL6 co-repressor, BCOR, is a ubiquitously expressed nuclear protein which directly interfaces to proto-oncoprotein BCL6. BCOR also associates with HDACs, the polycomb group protein PCGF1/NSPC1 and the histone demethylase FBXL10, which implies that it could suppress gene transcription by epigenetic mechanisms.
Gene Name RARA
Location 17q12-21
Protein Wide expression; nuclear receptor; binds specific DNA sequences: HRE (hormone response elements); ligand and dimerization domain; role in growth and differentiation.

Result of the chromosomal anomaly

Hybrid gene
  Schematic diagram of RARA, BCOR and the BCOR-RARA fusion protein. The break point is indicated by the black line. Ankyrin repeats (ANK).
 
Transcript BCOR cDNA (isoform b; reference NM_001123384) from exons 1 to 12 to be fused to RARA exon 3. Full length chimeric fusion transcripts spanning from the start codon to 4948 nt of BCOR cDNA fused to RARA cDNA from exon 3 to the stop codon. A reciprocal chimeric cDNA of RARA-BCOR was not detected.
  
Fusion Protein
Description BCOR-RARA had a BCORBBD (498~514 aa), three Ankyrin repeats (1410~1509 aa) of BCOR, a DNA binding domain (DBD) derived from RARA (1557~1622 aa) and a ligand binding domain of RARA (1669~1888 aa).
Expression Localisation BCOR-RARA localized as two patterns; (I) diffusely in the nucleus as well as PML-RARA, (II) diffusely in the nucleus and aggregately in the cytoplasm. The subcellular localization of BCOR-RARA was clearly distinguishable from the punctuate pattern shown in the nucleus of BCOR-expressing cells.
Oncogenesis BCOR-RARA was found to possess common features with other RARA fusion proteins. These included: (I) the same break point in RARA cDNA; (II) self-association; (III) RXRA is necessary for BCOR-RARA to associate with the RARA responsive element; (IV) action in a dominant-negative manner on RARA transcriptional activation; (V) aberrant subcellular relocalization.
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

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. Epub 2010 Aug 31.
PMID 20807888
 

Citation

This paper should be referenced as such :
Yamamoto, Y
t(X;17)(p11;q21) BCOR/RARA
Atlas Genet Cytogenet Oncol Haematol. 2012;16(6):429-431.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0X17p11q21ID1594.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(X;17)(p11;q21) BCOR/RARA

External links

BCOR (Xp11.4) RARA (17q21.2)

BCOR (Xp11.4) RARA (17q21.2)

Mitelman databaset(X;17)(p11;q21) [Case List]    t(X;17)(p11;q21) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseBCOR/RARA [MCList]  BCOR (Xp11.4) RARA (17q21.2)
TICdbBCOR/RARA  BCOR (Xp11.4) RARA (17q21.2)
 
Disease databaset(X;17)(p11;q21) BCOR/RARA
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
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indexed on : Fri Jun 30 11:23:37 CEST 2017


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