High prevalence and clinical significance of oncogenic CD79B and MYD88 mutations in primary testicular diffuse large B‐cell lymphoma: A retrospective study in China

Abstract

Activating mutations in CD79B and myeloid differentiation primary response gene 88 (MYD88) have recently been found in a subset of activated B-cell–like subtype of diffuse large B-cell lymphoma (ABC-DLBCL). Primary testicular DLBCLs (PT-DLBCLs) have uniform activated B-cell–like subtype characteristics. However, the studies on the CD79B and MYD88 mutation in PT-DLBCL have been limited, and the clinical significance remains unclear. Therefore, in this study, we investigate the prevalence of CD79B and MYD88 mutations and their relation to clinical significance in a cohort of Chinese testicular DLBCL patients. We examined the mutational status of CD79B and MYD88 and both the gene amplification and protein expression of MYD88 in 18 cases of PT-DLBCL tissue samples. Sanger sequencing was performed to detect oncogenic CD79B and MYD88 mutations. MYD88 gene amplification and protein expression were analyzed by quantitative PCR and by immunohistochemistry, respectively. Immunophenotypically, MYD88 protein stain was positive in 88.89% (16/18) cases. Fourteen of 18 (77.78%) cases tested positive for p65 in the nucleus, indicating activation of the NFκB signaling pathway. Genetically, CD79B mutation was found in 8/18 (44.44%) cases, and the MYD88 L265P mutation was found in 11/18 (61.11%) cases. The MYD88 L265P mutation coexisted with a CD79B mutation in 6 cases, which constituted 75% of CD79B mutants and 54.5% of MYD88 L265P cases. Furthermore, MYD88 is significantly amplified in PT-DLBCL. However, the amplification status showed no correlation with its mutational status or protein expression. Both MYD88 and CD79B mutational status and expression of MYD88 showed no significant correlation with the patient's age, non-GCB/GCB subtype, Ann Arbor stage, p65 protein expression, and double expression of BCL-2 and c-MYC (P > .05). Survival analyses showed that patients with MYD88 L265P mutation and p65 expression had a significantly poorer OS (P < .05). We demonstrated a high prevalence of CD79B and MYD88 L265P mutation in PT-DLBCL, and MYD88 L265P and p65 protein expression was a significant prognostic indicator. Our results suggest that MYD88 and CD79B mutations are important drivers of immune-privileged site-associated DLBCL (IP-DLBCL) and potential therapeutic targets for personalized treatment. Keywords: diffuse large B-cell lymphoma (DLBCL); MYD88; NF-κB