BCL6 Alternative Breakpoint Region (ABR) Rearrangement Is Associated with Lymphomas with Follicular Morphology.
James M Ziai, Lisa Ma, Yasodha Natkunam, Daniel A Arber. Stanford University Medical Center, CA
Background: Rearrangements of the major breakpoint region (MBR) and alternative breakpoint region (ABR) of BCL6 are reportedly associated with diffuse large B-cell lymphoma (DLCL), grade 3b follicular lymphoma (FL) and t(14,18)-negative FL. This suggests diagnostic utility of BCL6 FISH. However, the frequency in other lymphoma subtypes has not been fully studied. We present the first study of ABR rearrangement frequency and assessment of its diagnostic utility in a broad spectrum of lymphomas.
Design: Our series included 227 total cases including cases of DLCL (45 cases), follicular grade 1 (FL1) (41), follicular and diffuse large cell (F&DLC) (18), follicular grade 3 (FL3) (35), follicular grade 2 (FL2) (31 cases) and non-follicular low-grade B cell lymphomas (NFBCL) (51 cases) diagnosed between 1969 and 2007. Interphase FISH using Vysis (Abbott Laboratories, Des Plaines, Illinois) dual color breakapart probes targeting the 3q27 ABR and MBR regions was performed on paraffin-embedded tissue sections and a specimen microarray to assess presence of ABR or MBR translocation or trisomy 3. A translocation or trisomy was reported positive if present in >10% of cells. Controls included normal lymphoid tissue (lymph node, spleen, tonsil) as well as cases of non-lymphoid neoplasms.
Results: Although less frequent than BCL6 MBR translocations, which were present in 13% of all follicular lymphoma cases, cases of both t(14;18)-positive and -negative follicular lymphoma showed BCL6 ABR rearrangements (5.8% and 4.5%, respectively) as did FL2 (5.6%), FL3 (5%) and FL1 (4.5%). ABR rearrangement was absent in all DLCL and F&DLC cases compared to a 9.4% and 23.5% respective frequency of BCL6 MBR translocations. Also, trisomy 3 was observed in 2.6% of DLCL and 5.6% of F&DLC cases while absent in ABR rearrangement-positive FL2 cases. Interestingly, BCL6 MBR translocations were absent in all cases of FL1 while 10.5% of FL1 cases were ABR positive and 4.5% showed trisomy 3. MBR and ABR rearrangements as well as trisomy 3 were not observed in any normal lymphoid tissue or NFBCL.
Conclusions: Our results are the first to characterize prevalence of BCL6 ABR and MBR rearrangements in a large series of FL and non follicular B cell lymphomas. We have shown that ABR is found in both t(14;18) positive and negative FL and appears to be more frequent in FL1 than MBR translocations. In addition, unlike BCL6 MBR translocations, ABR translocations appear to be uncommon in DLCL, F&DLC. These data suggest diagnostic utility of ABR FISH in lymphomas with follicular morphology.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 205, Wednesday Afternoon