Characterization of chromosome 11 translocation breakpoints at the bcl-1 and PRAD1 loci in centrocytic lymphoma.
The chromosome 11q13 bcl-1 locus is rearranged in the majority of centrocytic lymphomas, a CD5-positive B-cell non-Hodgkins lymphoma, as a result of reciprocal translocation with the 14q32 immunoglobulin heavy chain genes. Although several 11q13 bcl-1 breakpoint sites have been characterized, a postulated bcl-1 oncogene was not identified. Recently, however, a gene encoding cyclin D1, designated PRAD1, was proposed as a candidate bcl-1 oncogene; accumulated evidence now indicates this gene is bcl-1. To further characterize 11q13 breakpoints in B-cell neoplasms, we analyzed 26 centrocytic lymphomas and 68 other B-cell cancers by Southern blot using a panel of breakpoint probes spanning 110 kilobases of the bcl-1 and PRAD1 loci. Nineteen centrocytic cases (73%) showed rearrangement, 15 at bcl-1 breakpoint sites and 5 at PRAD1 sites. One case was rearranged at both bcl-1 and PRAD1 loci. All but the latter case showed comigration of rearranged bcl-1 or PRAD1 bands and immunoglobulin heavy chain joining gene bands, consistent with the t(11;14). bcl-1 rearrangement was present in only one of 68 noncentrocytic B-cell neoplasms; none showed PRAD1 rearrangement. Thus, bcl-1 and PRAD1 rearrangement is strongly associated with centrocytic lymphoma, providing a useful molecular marker for classifying this subtype of lymphoma and suggesting an important role for PRAD1 cyclin D1 in the pathogenesis of this neoplasm.
Williams
M E
ME
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Swerdlow
S H
SH
Rosenberg
C L
CL
Arnold
A
A
D002880:Chromosomes, Human, Pair 11 / Q000737:chemistry*; D002883:Chromosomes, Human, Pair 14 / Q000737:chemistry*; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D015257:DNA-Cytosine Methylases / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014178:Translocation, Genetic
D016213:Cyclins; D015342:DNA Probes; D004273:DNA, Neoplasm; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C042525:DNA modification methylase BamHI; D015257:DNA-Cytosine Methylases