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The CBFA2T3/ACSF3 locus is recurrently involved in IGH chromosomal translocation t(14;16)(q32;q24) in pediatric B‐cell lymphoma with germinal center phenotype
Author(s) -
Salaverria Itziar,
Akasaka Takashi,
Gesk Stefan,
Szczepanowski Monika,
Burkhardt Birgit,
Harder Lana,
DammWelk Christine,
Oschlies Ilske,
Klapper Wolfram,
Dyer Martin J. S.,
Siebert Reiner
Publication year - 2012
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.21919
Subject(s) - chromosomal translocation , biology , germinal center , lymphoma , follicular lymphoma , fluorescence in situ hybridization , b cell , population , gene rearrangement , microbiology and biotechnology , cancer research , genetics , gene , antibody , immunology , chromosome , medicine , environmental health
Translocations involving immunoglobulin ( IG ) loci are the hallmarks of several subtypes of B‐cell lymphoma. Common to these translocations is that cellular proto‐oncogenes come under the influence of IG regulatory elements leading to deregulated expression. In case of a breakpoint in the IGH switch region, oncogene activation can take place on both derivative chromosomes, which means that in principle one translocation can result in concurrent activation of two genes. By fluorescence in situ hybridization (FISH), we identified a case of leukemic B‐cell lymphoma in a child with an IGH break and unknown partner. Subsequent long‐distance inverse PCR revealed fusion of IGH Sμ in 14q32 and the 5′ region of CBFA2T3 in 16q24.3, suggesting presence of the t(14;16)(q32;q24.3). Candidate oncogenes targeted through this translocation are CBFA2T3 and ACSF3 , which could be activated on der(16) and der(14), respectively. FISH screening of a population‐based cohort of B‐cell lymphomas from a prospective trial for the treatment of lymphoma in childhood (BFM‐NHL) identified additionally a follicular lymphoma Grade 3/diffuse large B‐cell lymphoma with IGH‐CBFA2T3/ACSF3 juxtaposition. Both lymphomas shared expression of CD10 and CD20 in the absence of TdT, suggesting a germinal center (GC) B‐cell origin. Our data indicate that the CBFA2T3/ACSF3 locus is a novel recurrent oncogenic target of IGH translocations, which might contribute to the pathogenesis of pediatric GC‐derived B‐cell lymphoma. © 2011 Wiley Periodicals, Inc.