Alternative translocation breakpoint cluster region 5' to BCL-6 in B-cell non-Hodgkin's lymphoma.
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.
Butler
Marion P
MP
Institute for Cancer Genetics, and the Department of Pathology, Columbia University, New York, NY 10032, USA.
Iida
Shinsuke
S
Capello
Daniela
D
Rossi
Davide
D
Rao
Pulivarthi H
PH
Nallasivam
Palanisamy
P
Louie
Diane C
DC
Chaganti
Seeta
S
Au
Thomas
T
Gascoyne
Randy D
RD
Gaidano
Gianluca
G
Chaganti
Raju S K
RS
Dalla-Favera
Riccardo
R
D001483:Base Sequence; D019457:Chromosome Breakage; D002883:Chromosomes, Human, Pair 14; D002893:Chromosomes, Human, Pair 3; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors