''Minor'' BCL2 breakpoints in follicular lymphoma: frequency and correlation with grade and disease presentation in 236 cases.
Follicular lymphomas are frequently associated with the t(14;18)(q32;q21). This translocation can be detected by karyotype, polymerase chain reaction (PCR), and fluorescence in situ hybridization (FISH). In addition to the breakpoints currently used for diagnosis located in the major breakpoint region (MBR) and the minor cluster region (mcr), recent studies have reported the existence of other breakpoints (3' BCL2, 5'mcr, and icr). In this study, we examined the frequency of all five breakpoints in 236 cases of follicular lymphomas by real-time PCR analysis. The distribution of breakpoint sites consisted of MBR in 118 cases (50%), mcr in 11 (5%), icr in 32 (13%), 3' BCL2 in 13 (6%), and 5' mcr in three cases (1%). These findings illustrate significantly higher frequency of the icr breakpoint as compared with the more frequently studied mcr. Correlation of breakpoints with histology showed that MBR breakpoints occur more frequently in grade 2 lymphomas (P = 0.042). A majority of the PCR-negative cases (75%) contained an IGH/BCL2 translocation with FISH methods, suggesting the presence of other BCL2 breakpoints. Correlation of breakpoints with survival did not reveal significant differences. Diagnostic laboratories should consider expanding their PCR methods to include other BCL2 breakpoints and correlating with FISH methods when appropriate.
Weinberg
Olga K
OK
Stanford University, Department of Pathology, 300 Pasteur Dr., Room L235, Stanford, CA 94305, USA. okw@stanford.edu
Ai
Weiyun Z
WZ
Mariappan
M Rajan
MR
Shum
Carol
C
Levy
Ronald
R
Arber
Daniel A
DA
D019457:Chromosome Breakage; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D016133:Polymerase Chain Reaction; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D016019:Survival Analysis; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6