Alternative translocation breakpoint cluster region 5' to BCL-6 in B-cell non-Hodgkin's lymphoma.
2002; National Institutes of Health; Volume: 62; Issue: 14 Linguagem: Inglês
Autores
Marion Butler, Shinsuke Iida, Daniela Capello, Davide Rossi, Pulivarthi H. Rao, Nallasivam Palanisamy, Diane C. Louie, Seeta R. Chaganti, Thomas Chi Chuen Au, Randy D. Gascoyne, Gianluca Gaïdano, R. S. K. Chaganti, Riccardo Dalla‐Favera,
Tópico(s)T-cell and Retrovirus Studies
ResumoChromosomal translocations involving band 3q27 with various different partner chromosomes represent a recurrent cytogenetic abnormality in B-cell non-Hodgkin's lymphoma. In a fraction of these translocations, the chromosomal breakpoint is located within the 5' noncoding region of the BCL-6 proto-oncogene where the BCL-6 major breakpoint region (MBR) maps. As a result of the translocation, BCL-6 expression is deregulated by promoter substitution. However, between 30 and 50% of lymphomas with cytogenetically detectable translocations affecting band 3q27 retain a germ-line configuration at the BCL-6 locus. To identify possible additional breakpoint clusters within 3q27, we cloned a t(3;14)(q27;q32) lymphoma without MBR rearrangement and found a novel breakpoint site located between 245 and 285 kb 5' to BCL-6. Breakpoints within this newly described region, which we called the alternative breakpoint region (ABR), were found to be recurrent in lymphomas carrying t(3q27) chromosomal translocations but devoid of BCL-6 MBR rearrangements. Comparative analysis of multiple lymphomas carrying rearrangements within the ABR showed that the breakpoints cluster within a 20-kb distance. Translocations involving the ABR may juxtapose BCL-6 to distantly acting, heterologous transcriptional regulatory elements which cause deregulation of the proto-oncogene. The identification of BCL-6 ABR provides new tools for the diagnosis of lymphomas carrying aberrations at 3q27 and deregulated BCL-6 genes.
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