The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma

被引：19

作者：

Penas, Eva Maria Murga ^{[1
]}

Callet-Bauchu, Evelyne ^{[2
]}

Ye, Hongtao ^{[3
]}

Gazzo, Sophie ^{[2
]}

Berger, Francoise ^{[2
]}

Schilling, Georgia ^{[1
]}

Albert-Konetzny, Nadine ^{[1
]}

Vettorazzi, Eik ^{[4
]}

Salles, Gilles ^{[2
]}

Wlodarska, Iwona ^{[5
]}

Du, Ming-Qing ^{[3
]}

Bokemeyer, Carsten ^{[1
]}

Dierlamm, Judith ^{[1
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Hubertus Wald Tumorzentrum Univ Canc Ctr Hamburg, Dept Hematol & Oncol, BMT Sect Pneumol, D-20246 Hamburg, Germany

[2] Ctr Hosp Lyon Sud, Dept Pathol & Hematol, Lyon, France

[3] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England

[4] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany

[5] Univ Leuven, Ctr Human Genet & Flanders Interuniv, Inst Biotechnol, Louvain, Belgium

来源：

BLOOD | 2010年 / 115卷 / 11期

关键词：

DOUBLE-STRAND BREAKS; CHROMOSOMAL TRANSLOCATIONS; V(D)J RECOMBINATION; T(14/18) TRANSLOCATION; MECHANISM; REPAIR; IGH; T(11/18)(Q21; Q21); T(1/14)(P22; Q32); ABERRATION;

D O I：

10.1182/blood-2009-08-236265

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence-guided V(D) J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D) J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D) J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner. (Blood. 2010;115:2214-2219)

引用

页码：2214 / 2219

页数：6

共 28 条

[1] MECHANISM OF THE T(14-18) CHROMOSOMAL TRANSLOCATION - STRUCTURAL-ANALYSIS OF BOTH DERIVATIVE-14 AND DERIVATIVE-18 RECIPROCAL PARTNERS [J].