Clinical Significance of CMYC Rearrangement in Diffuse Large B-Cell Lymphoma.
Gabriel C Caponetti, Bhavana Dave, Lynette Smith, Paul Meyer, Martin Bast, Philip Bierman, Gregory Bociek, Julie Vose, James O Armitage, Patricia Aoun, Kai Fu, Timothy Greiner, Wing C Chan, Dennis Weisenburger. University of Nebraska Medical Center, Omaha
Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of B-cell lymphomas with a wide variation in prognosis, due in part to various genetic abnormalities. Rearrangements of the CMYC oncogene are seen in up to 10% of patients with DLBCL, but the prognostic importance of this abnormality is unclear. Another oncogene often rearranged in DLBCL is BCL2. Since both CMYC and BCL2 are dominant oncogenes whose expression in DLBCL plays an important pathogenetic role, expression of both may have a synergistic effect leading to poor survival. To test this hypothesis, we performed a retrospective analysis of DLBCL cases tested for translocations involving CMYC and BCL2 and treated with CHOP or R-CHOP-like therapy.
Design: We conducted a search of the Nebraska Lymphoma Study Group database for all cases of de novo DLBCL with available clinical data, patient consent, no pretreatment, and available conventional cytogenetics and/or fluorescence in situ hybridization (FISH) results. Patients with a history of HIV infection or organ transplantation were excluded. Conventional cytogenetic and/or FISH reports were analyzed to identify rearrangements of CMYC and/or BCL2. Based on the rearrangement of these two genes, cases of DLBCL were classified into 3 groups: CMYC+/BCL2+, CMYC+/BCL2- and CMYC- (with or without BCL2 rearrangement). The 5-year overall survival (OS) of the 3 groups was compared.
Results: We identified 216 cases of DLBCL with a male:female ratio of 1:1 and a median age at diagnosis of 66.1 years (range 20.4 to 90.3 years). Based on the rearrangement of CMYC and/or BCL2 genes, the cases of DLBCL were classified into 3 groups: 11 cases (5%) were CMYC+/BCL2+ (5-year OS 28%), 14 cases (6.5%) were CMYC+/BCL2- (5-year OS 64%) and 191 cases (88.5%) were CMYC- (with or without BCL2 rearrangement) (5-year OS survival 48%). No significant differences in clinical characteristics were identified among the groups except for increased development of B-symptoms in the CMYC+/BCL2- group. A decreased complete remission rate and a trend towards a worse OS were identified in the CMYC+/BCL2+ group.
Conclusions: Cases of DLBCL with CMYC rearrangement but no BCL2 rearrangement are not associated with a significantly different OS when compared with cases of DLBCL with no rearrangement of CMYC. However, cases of DLBCL with both CMYC and BCL2 rearrangements have a poorer complete remission and a trend towards worse outcome.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 183, Monday Morning