This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Butler, M. P. Articles by Dalla-Favera, R. Search for Related Content PubMed PubMed Citation Articles by Butler, M. P. Articles by Dalla-Favera, R.

Alternative Translocation Breakpoint Cluster Region 5' to BCL-6 in B-cell Non-Hodgkin’s Lymphoma¹

Institute for Cancer Genetics, and the Departments of Pathology and Genetics & Development, Columbia University, New York, NY 10032 [M. P. B., S. I., R. D-F.]; Hematology Unit, Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, 28100 Novara, Italy [D. C., D. R., G. G.]; Cell Biology and Genetics Programs, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [P. H. R., P. N., D. C. L., S. C., R. S. K. C.]; and the Department of Pathology, British Columbia Cancer Agency, Vancouver, V5Z 4E6 Canada [T. A., R. D. G.]

Chromosomal 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.

This article has been cited by other articles:

				Y.-W. Chen, X.-T. Hu, A. C. Liang, W.-Y. Au, C.-C. So, M. L. Wong, L. Shen, Q. Tao, K.-M. Chu, Y.-L. Kwong, et al. High BCL6 expression predicts better prognosis, independent of BCL6 translocation status, translocation partner, or BCL6-deregulating mutations, in gastric lymphoma Blood, October 1, 2006; 108(7): 2373 - 2383. [Abstract] [Full Text] [PDF]

				H. Niu, G. Cattoretti, and R. Dalla-Favera BCL6 Controls the Expression of the B7-1/CD80 Costimulatory Receptor in Germinal Center B Cells J. Exp. Med., July 21, 2003; 198(2): 211 - 221. [Abstract] [Full Text] [PDF]

				P. Pevzner and G. Tesler Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution PNAS, June 24, 2003; 100(13): 7672 - 7677. [Abstract] [Full Text] [PDF]

				L. Pasqualucci, A. Migliazza, K. Basso, J. Houldsworth, R. S. K. Chaganti, and R. Dalla-Favera Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma Blood, April 15, 2003; 101(8): 2914 - 2923. [Abstract] [Full Text] [PDF]