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t(2;14)(p13-16;q32) IGH/BCL11A

Written2002-06Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France
Updated2010-02Adriana Zamecnikova
Kuwait Cancer Control Center, Laboratory of Cancer Genetics, Department of Hematology, Shuwaikh, 70653, Kuwait

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1231
 
  (A) Partial karyotype showing the t(2;14)(p13;q32) Top - Courtesy Adriana Zamecnikova; Middle and below - Courtesy Melanie Zenger and Claudia Haferlach. (B) Fluorescence in situ hybridization with LSI IgH/MYC and LSI ALK probe showing the juxtaposition of ALK (fusion signal) from 2p23 to the region proximal to IgH locus (green signal) on chromosome 14 and translocation of IgH segments to der(2) chromosome resulting in a green signal on rearranged chromosome 2 - Courtesy Adriana Zamecnikova.

Clinics and Pathology

Disease Identified predominantly in B-cell malignancies, including CLL/SLL, found in 20 cases of chronic lymphocytic leukemia (CLL), 1 B-prolymphocytic leukemia, 1 diffuse, mixed small/large cell non Hodgkin lymphoma (NHL); 8 cases of acute lymphocytic leukemia (ALL): one T-ALL and 7 B-ALL (two in association with t(1;19), one in Ph+ ALL, one with 3-way translocation); two AML (Ph+ M1 and inv(16)) cases and in one Ph+ CML case.
CLL cases are characterized by marrow involvement, absolute lymphocytosis, lymphadenopathy, atypical morphologic features; prolymphocytes may be increased. Serum lactate dehydrogenase and beta-microglobulin levels are elevated, ZAP70 is expressed.
IgVH genes are unmutaded; most cases are positive for CD5, CD19 and CD23; weak intensity of immunoglobuline and CD20, weak or negative CD79b, CD22, absence of FMC-7.
Epidemiology Sex ratio: CLL cases 10 males and 6 females patients, 4 unknown; adults : aged 40-68 years,, and 3 children aged 6, 10 and 15 years; ALL cases (3 males, 5 females) were 1 adult 37 years old and 7 children aged 1-17 years; 2 AML cases (1 male, 1 female) were 34 and 45 years old; the CML case was a 21 years old male patient.
Prognosis 8 CLL cases were dead after 27-145 months survival; from available data on 3 ALL cases : the y were all dead (one after 15 months, 2 after bone marrow transplantation).

Cytogenetics

Cytogenetics Morphological Sole anomaly in 8 documented cases; found in complex karyotypes; associated with t(14;19)(q32;q13) in 2 CLL cases, del(6)q in 4 cases, i(9)(q10) in 2 cases, +12 in 3 cases. In two pediatric ALL cases, it was associated with t(1;19) and in 3 cases it was associated with Ph+ leukemia.

Genes involved and Proteins

Gene NameBCL11A (B-cell lymphoma/leukemia 11A)
Location 2p16.1
Dna / Rna Originally assigned to region 1, band 3, 2p13; it has subsequently been reassigned to 2p16.1.
Protein BCL11A/EVI9 is a zinc-finger protein, containing 6 Krüppel C2H2 zinc fingers as well as a proline-rich domain between zinc fingers 1 and 2 and an acidic domain between 3 and 4. 835 amino acids; 91197 Da, alternative splicing: 6 isoforms, sharing a common N-terminus. Originally named EV19 human homolog BCL11A; high level of conservation across a wide range of species; highly homologous to another gene (BCL11B) on chromosome 14q32.1; like BCL11A, BCL11B is remarkable in having a large 5' CpG island. Predominantly expressed in brain and hematopoietic cells, expression is tightly regulated during B-cell development; low-level or undetectable BCL11A RNA expression in most adult tissues. BCL11A is a DNA sequence-specific transcriptional repressor, an essential factor in lymphopoiesis, required for B-cell formation in fetal liver.
Gene NameIGH (Immunoglobulin Heavy)
Location 14q32.33

Result of the chromosomal anomaly

Fusion Protein
Oncogenesis Juxtaposition of IgH enhancer elements leading to inappropriate overexpression of the partner gene product. BCL11A may be activated through chromosomal translocation or amplification, leading to myeloid leukemias in mice and lymphoid malignancies in humans; the conserved N-terminus of BCL11A. deregulated expression of BCL11A may play a major role in the pathogenesis; gains and amplifications of the region of chromosome 2p13-16 have been reported in B-cell malignancies, REL, a NF-kappaB gene family member, mapping within the amplified region is coamplified with BCL11A in B-NHL cases and HD lymphoma cell lines; with gains and amplifications, BCL11A interacts directly with BCL6, that serves a crucial role in lymphocyte development, also involved in IG translocations.
The structure of the t(2;14) translocation is a "head-to-head" arrangement, with the breakpoints falling centromeric to the first exon adjacent to a large CpG island at the 5' end; BCL11A is deregulated as a consequence of the translocation, suggesting that BCL11A may be involved in lymphoid malignancies through either chromosomal translocation or amplification.
  

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

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.
Geisler CH, Philip P, Christensen BE, Hou-Jensen K, Pedersen NT, Jensen OM, Thorling K, Andersen E, Birgens HS, Drivsholm A, Ellegaard J, Larsen JK, Plesner T, Brown P, Andersen PK, Hansen MM.
Leuk Res. 1997 Nov-Dec;21(11-12):1011-23.
PMID 9444933
 
Nonrandom rearrangement of chromosome 14 at band q32.33 in human lymphoid malignancies with mature B-cell phenotype.
Nishida K, Taniwaki M, Misawa S, Abe T.
Cancer Res. 1989 Mar 1;49(5):1275-81.
PMID 2492904
 
The BCL11 gene family: involvement of BCL11A in lymphoid malignancies.
Satterwhite E, Sonoki T, Willis TG, Harder L, Nowak R, Arriola EL, Liu H, Price HP, Gesk S, Steinemann D, Schlegelberger B, Oscier DG, Siebert R, Tucker PW, Dyer MJ.
Blood. 2001 Dec 1;98(12):3413-20.
PMID 11719382
 
A plasma cell leukemia patient showing bialleic 14q translocations: t(2;14) and t(11;14).
Sonoki T, Matsuzaki H, Satterwhite E, Nakazawa N, Hata H, Tucker PW, Taniwaki M, Kuribayashi N, Harada N, Matsuno F, Mitsuya H.
Acta Haematol. 1999;101(4):197-201.
PMID 10436301
 
Immunophenotype-karyotype associations in human acute lymphoblastic leukemia.
Uckun FM, Gajl-Peczalska KJ, Provisor AJ, Heerema NA.
Blood. 1989 Jan;73(1):271-80.
PMID 2910365
 
A 14;19 translocation in B-cell chronic lymphocytic leukemia: a new recurring chromosome aberration.
Ueshima Y, Bird ML, Vardiman JW, Rowley JD.
Int J Cancer. 1985 Sep 15;36(3):287-90.
PMID 3875568
 
t(2;14)(p13;q32): a recurring abnormality in lymphocytic leukemia. A Pediatric Oncology Group study.
Watson MS, Land VJ, Carroll AJ, Pullen J, Borowitz MJ, Link MP, Amylon M, Behm FG.
Cancer Genet Cytogenet. 1992 Feb;58(2):121-4.
PMID 1551073
 
Chronic lymphocytic leukemia With t(2;14)(p16;q32) involves the BCL11A and IgH genes and is associated with atypical morphologic features and unmutated IgVH genes.
Yin CC, Lin KI, Ketterling RP, Knudson RA, Medeiros LJ, Barron LL, Huh YO, Luthra R, Keating MJ, Abruzzo LV.
Am J Clin Pathol. 2009 May;131(5):663-70.
PMID 19369625
 
Childhood chronic lymphocytic leukemia with (2;14) translocation.
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J Pediatr. 1990 Jan;116(1):114-7.
PMID 2295951
 

Citation

This paper should be referenced as such :
Zamecnikova, A
t(2;14)(p13-16;q32)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(11):1082-1084.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0214p13q32ID1231.html
History of this paper:
Huret, JL. t(2;14)(p13;q32). Atlas Genet Cytogenet Oncol Haematol. 2002;6(4):291-292.
http://documents.irevues.inist.fr/bitstream/handle/2042/37900/06-2002-t0214p13q32ID1231.pdf


Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes BCL11A

Translocations implicated (Data extracted from papers in the Atlas)

 t(2;14)(p13;q32) IGH/BCL11A

External links

IGH (14q32.33) BCL11A (2p16.1)

Mitelman databaset(2;14)(p13;q32) [Case List]    t(2;14)(p13;q32) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9837/3) - 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]
 
Mitelman databaseIGH/BCL11A [MCList]  IGH (14q32.33) BCL11A (2p16.1)
 
Disease databaset(2;14)(p13-16;q32) IGH/BCL11A
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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