CD79B Mutation in Diffuse Large B-Cell Lymphoma
Yuil Kim, Hyunjung Ju, Dong-Hoon Kim, Young-Hyeh Ko. Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea; Hallym University Sacred Heart Hospital, Anyang, Gyeonggi-do, Republic of Korea
Background: Activation of nuclear factor kB (NF-kB) pathway is an important tumorigenic mechanism in the activated B cell-like (ABC) diffuse large B-cell lymphoma (DLBCL). Mutation of CD79B, a B-cell receptor component, has been identified in DLBCL, which was proposed to contribute to the chronic active B-cell receptor signaling leading to NF-kB activation (Davis et al, Nature, 463:88, 2010). With the advent of several drugs blocking the B-cell receptor signaling pathway, we sought to assess the frequency of CD79B mutation in DLBCL cases and its prognostic effect.
Design: CD79B gene was sequenced in the immunoreceptor tyrosine-based activation motif (ITAM) for 187 DLBCL tissue samples, which were categorized as ABC (n=131) or germinal center B cell-like (GCB, n=56) according to Hans' algorithm based on immunohistochemistry.
Results: Eighteen point mutations were identified (9.6% of 187), 14 of which were missense mutations affecting the first ITAM tyrosine. The proportions of CD79B mutants in the ABC and GCB group were not significantly different (10% vs. 5%, p=0.4). For other clinicopathologic factors, the CD79B mutant showed older age (65 vs. 58 years, p=0.03) and lower proportion of gastrointestinal tract (GI) origin (13% vs. 32%, p=0.15) than the wild type, but no difference was found in other factors, such as sex, international prognostic index (IPI), and treatment response. The Kaplan-Meier curves for the overall and progression-free survival comparing the CD79B mutant and wild type crossed and gave insignificant differences (p=0.8 for each). However, high IPI and non-GI origin were significantly associated with worse survival. Older age (>60 years) and ABC type showed worse, but insignificant (p=0.14 and 0.11), survival on univariate analyses. On multivariate analyses using Cox proportional hazards model adjusting for age, GI origin, IPI and ABC/GCB type, the CD79B mutant exhibited slightly better overall (HR 0.9, p=0.8) and progression-free (HR 0.7, p=0.4) survival than the wild type, although not significant.
Conclusions: Compared with the previous report (Davis et al, 2010), we found lower frequency of CD79B ITAM mutations in DLBCL, and the mutation was not significantly predominant in the ABC type. The presence of CD79B mutation was not a significant prognostic factor for DLBCL, although a slight improvement in survival was suggested.
Monday, March 4, 2013 1:00 PM
Poster Session II # 188, Monday Afternoon