Primary Extranodal Diffuse Large B-Cell Lymphomas Are Enriched for Mutations in MYD88 and CD79B.

Abstract

Introduction: Diffuse large B-cell lymphomas (DLBCLs) with mutations in MYD88 and CD79B are a distinct molecular subentity according to recent analysis (“MCD-type” according to R. Schmitz et al., N Engl J Med 2018; and partially “cluster 5” according to B. Chapuy et al., Nature Medicine 2018). Both mutations were found particularly in specific anatomical localizations.Methods: To evaluate the incidence of MYD88 and CD79B mutations in primary extranodal DLBCL, we analyzed 111 tumor specimens of 99 patients. We performed targeted resequencing analysis to detect MYD88, CD79B, CARD11 and BTK mutations.Results:MYD88 mutations were frequently found in primary CNS lymphoma (67%), lymphoma of Waldeyer´s ring and paranasal sinuses (ENT) (44%), breast (75%), testicular (60%) and cutaneous (50%); the majority of mutations (89%) were located on L265P. CD79B mutations were frequent in CNS lymphoma (57%), lymphoma of ENT (52%) and breast lymphoma (50%). Both mutations occur simultaneously in CNS lymphoma (48%) and ENT lymphoma (33%). CARD11 mutations were frequently found in CNS lymphoma (33%) and in ENT lymphoma (26%). BTK mutations were found rarely, with the highest frequency (11%) in ENT lymphoma.Conclusion: Both, mutations in CD79B and MYD88 are frequent in primary extranodal lymphoma particularly in CNS lymphoma, lymphoma of Waldeyer's ring and paranasal sinuses, testicular, cutaneous and breast lymphoma. These findings may contribute to establish targeted therapeutic intervention of B-cell signaling in this subentity. [Display omitted] DisclosuresWeissinger:Bristol-Myers Squibb: Research Funding. Viardot:BMS: Consultancy, Honoraria; Gilead Kite: Consultancy, Honoraria; Amgen: Consultancy; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.