Somatic Mutations of CD79A/B and EZH2 in a Series of DLBCL
Laura Comerma Blesa, Mar Garcia-Garcia, Anna Puiggros, Concepcion Fernandez-Rodriguez, Beatriz Casado, Maria Rodriguez, Marta Salido, Ana Ferrer, Blanca Sanchez-Gonzalez, Antonio Salar, Blanca Espinet, Beatriz Bellosillo, Sergi Serrano. Hospital del Mar, Barcelona, Spain
Background: Somatic mutations affecting the immunoreceptor tyrosine-based activation motif signaling modules of CD79A and CD79B and the polycomb-group oncogene enhancer of zeste homolog 2 (EZH2) have been identified in the last years in different subgroups of diffuse large B cell lymphoma (DLBCL). The CD79A/B heterodimer is essential for the assembly and membrane expression of the B cell receptor and initiates downstream signaling pathways. Somatic mutations affecting CD79A/B are detected frequently in Activated B-cell (ABC) DLBCL (18%) but rarely in other types of DLBCLs. On the other hand, the polycomb group protein EZH2 is a histone methyltransferase that associates with transcriptional repression. Mutations affecting the EZH2 oncogene, have been reported to occur in Germinal Center (GCB) DLBCLs (21%) and to be absent from ABC DLBCLs.
Design: We analyzed the mutational status of CD79A/B and EZH2 by Sanger sequencing in a series of 87 DLBCL diagnosed at our institution between 2000 and 2012 according to WHO 2008 diagnostic criteria for lymphomas. In all cases, immunohistochemical studies, including CD20, CD3, CD10, Bcl6, MUM1, Bcl2 and Ki67 had been previously tested for diagnostic purposes. In 47 cases FISH studies for either BCL2, BCL6 or MYC oncogenes had been also previously performed.
Results: Eighty-seven cases of DLBCL (46 male; 41 female) with a median age of 69 years (range 22-94) were included in the study. Forty-five cases were of GCB type (51.7%) and 42 cases of ABC type (48.3%). 15 out of 87 cases correspond to “double hit” or “triple hit” (DH/TH) lymphomas showing at least two translocations in either BCL2, BCL6 and/or MYC oncogenes, and GCB phenotype. No mutations in CD79A were detected in any of the 72 cases tested, whereas CD79B was mutated in 4/72 cases (5%) (2 GCB and 2 ABC). EZH2 gene was mutated in 12/87 cases (14%), but more frequently in GCB type (9 GCB vs 3 ABC), and a marginally significant correlation was found between EZH2 mutations and BCL2 rearrangements (p. 0.058).
|BCL2 Rearranged||BCL2 Not Rearranged|
|EZH2 Not Mutated||11||18|