BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphomas (DLBCL)
N Akyurek, A Uner, M Benekli, I Barista. Gazi University, Medical Faculty, Ankara, Turkey; Hacettepe University, Medical Faculty, Ankara, Turkey
Background: DLBCL is a biologically heterogeneous group in which various chromosomal translocations and gene alterations have been reported. The aim of this study was to investigate the copy number variations and translocations involving BCL2, BCL6 and MYC genes in adult DLBCLs.
Design: Tissue microarrays were constructed from 242 cases of DLBCL and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. Alterations in BCL2, BCL6 and MYC were investigated by using breakapart fluorescence in situ hybridization (FISH) probes on tissue microarrays. Clinical follow-ups were obtained from patient records and correlations among various parameters were evaluated by using statistical analysis.
Results: The DLBCL cases included 118 male and 124 female patients with an age range of 16-95 years (median age, 56 years). A GCB phenotype was found in 49% and non-GCB in 51% of the tumors as defined by the Hans' algorithm. BCL2 rearrangement was observed in 15% (36/242) and amplification in 25% (60/242) of the cases. BCL6 rearrangement was detected in 28% (68/242) and amplification in 20% (48/242). MYC rearrangement was observed in 6% (15/242) and amplification in 16% (39/242). There was no correlation between GCB and non-GCB profile cases with regards to BCL2, BCL6 and MYC rearrangements. Double translocations were detected in 3% of DLBCL cases: concurrent BCL2/MYC rearrangement in 4 cases, and BCL6/MYC in 2 cases. An additional case showed rearrangements involving all three genes (BCL2/BCL6/MYC). All of these cases had a high proliferation rate (Ki-67 > 80%). The prognosis of the cases with dual or triple translocations was extremely poor with a median survival of 9 months and overall survival rate of 14%. MYC rearrangement was also associated with poor clinical outcome (69% versus 22%, p=0.001).
Conclusions: Analyses of BCL2, BCL6 and MYC are critical in identifying high grade B cell lymphomas with poor prognosis. In particular, cases with dual or triple translocations and cases with MYC alterations appear to have poor prognosis.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 176, Wednesday Morning