PMID- 19465899 OWN - NLM STAT- MEDLINE DCOM- 20091110 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Print) IS - 0893-3952 (Linking) VI - 22 IP - 9 DP - 2009 Sep TI - t(14;18)-negative follicular lymphomas are associated with a high frequency of BCL6 rearrangement at the alternative breakpoint region. PG - 1251-7 LID - 10.1038/modpathol.2009.81 [doi] AB - A frequent chromosomal translocation in mature B-cell non-Hodgkin lymphoma affects band 3q27 and results in the deregulation of the B-cell lymphoma 6 (BCL6) gene. Two breakpoint clusters have been described thus far, the major breakpoint region (MBR) and an alternative breakpoint region (ABR) that is located 245-285 kb 5' to BCL6. Translocation at the MBR predominates in diffuse large B-cell lymphoma, whereas translocation at the ABR is reported to be frequently associated with grade 3B follicular lymphoma. However, translocation at the ABR has not been studied in a large series of follicular lymphomas, particularly t(14;18)-negative follicular lymphomas. Therefore, we studied BLC6 rearrangements at the MBR and ABR by using break-apart fluorescence in situ hybridization (FISH) probes in 142 cases of follicular lymphomas, including 63 t(14;18)-negative and 79 t(14;18)-positive cases. Conventional cytogenetic (karyotype) analysis was also performed in 58 of the 63 t(14;18)-negative cases. BCL6 rearrangement was found in 26% of t(14;18)-negative and 19% of t(14;18)-positive follicular lymphoma. t(14;18)-negative cases showed a high frequency of rearrangement at the ABR (12%) with an ABR/MBR ratio of 0.86, compared with only 5% with an ABR/MBR ratio of 0.36 in the t(14;18)-positive cases. BCL6 rearrangements were found in all grades of follicular lymphoma but were most frequent in grade 3 t(14;18)-negative follicular lymphoma (60%). FISH analysis had a higher sensitivity for detecting BCL6 rearrangements than conventional cytogenetics. In conclusion, BCL6 rearrangements occur at a similar frequency in t(14;18)-negative follicular lymphoma and diffuse large B-cell lymphoma. However, t(14;18)-negative follicular lymphoma appears to have a higher frequency of rearrangement at the ABR compared with t(14;18)-positive follicular lymphoma and diffuse large B-cell lymphoma. Therefore, it is important to perform FISH analysis with ABR to determine possible involvement of BCL6 rearrangement in follicular lymphoma, especially in t(14;18)-negative cases. FAU - Gu, Keni AU - Gu K AD - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA. FAU - Fu, Kai AU - Fu K FAU - Jain, Smrati AU - Jain S FAU - Liu, Zhongfen AU - Liu Z FAU - Iqbal, Javeed AU - Iqbal J FAU - Li, Min AU - Li M FAU - Sanger, Warren G AU - Sanger WG FAU - Weisenburger, Dennis D AU - Weisenburger DD FAU - Greiner, Timothy C AU - Greiner TC FAU - Aoun, Patricia AU - Aoun P FAU - Dave, Bhavana J AU - Dave BJ FAU - Chan, Wing C AU - Chan WC LA - eng GR - U01 CA114778/CA/NCI NIH HHS/United States GR - U01 CA114778-03/CA/NCI NIH HHS/United States GR - 5U01/CA114778/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20090522 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (BCL6 protein, human) RN - 0 (DNA-Binding Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-6) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Chromosome Breakage MH - Chromosomes, Human, Pair 14/genetics MH - Chromosomes, Human, Pair 18/genetics MH - DNA-Binding Proteins/*genetics MH - Female MH - *Gene Rearrangement MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lymphoma, Follicular/*genetics MH - Lymphoma, Large B-Cell, Diffuse/genetics MH - Male MH - Middle Aged MH - Proto-Oncogene Proteins c-bcl-6 MH - Translocation, Genetic/genetics PMC - PMC2736319 MID - NIHMS111999 EDAT- 2009/05/26 09:00 MHDA- 2009/11/11 06:00 PMCR- 2010/03/01 CRDT- 2009/05/26 09:00 PHST- 2009/05/26 09:00 [entrez] PHST- 2009/05/26 09:00 [pubmed] PHST- 2009/11/11 06:00 [medline] PHST- 2010/03/01 00:00 [pmc-release] AID - S0893-3952(22)02478-4 [pii] AID - 10.1038/modpathol.2009.81 [doi] PST - ppublish SO - Mod Pathol. 2009 Sep;22(9):1251-7. doi: 10.1038/modpathol.2009.81. Epub 2009 May 22.