Distribution and influencing factors of tumor mutational burden in different lymphoma subtypes.

Abstract

e19053 Background: Tumor mutational burden (TMB) has emerged as a promising biomarker in melanoma, NSCLC, glioma, and likely across types of solid cancers. However, TMB distribution and influencing factors in non-Hodgkin's lymphoma are still unknown. Methods: In this study, we focused on tumor (tTMB) and peripheral blood TMB (bTMB) in different lymphoma subtypes and conducted a hybridization-capture methodology and targeted 1.1Mb or 1.7 Mb of genomic coding sequence. Analysis of 188 tumors and 98 plasma samples matching oral epithelial normal samples was performed to characterize the landscape of somatic mutations between the TMB high (TMB-H) and TMB low (TMB-L) groups. Results: In our cohort, tTMB and bTMB ranged from 0 to 42.48, and 0.59 to 37.17, respectively. The top quartile TMB distribution (tTMB:12.34, bTMB:13.20) was used as the cut-off value to define TMB-H. DLBCL had significantly higher tTMB than small B cell lymphoma and peripheral T-cell lymphoma (p < 0.0001). 34.09% of DLBCL had TMB-H, and minority of patients had TMB-H in small B cell lymphoma (3.70%), and peripheral T-cell lymphoma (3.85%). The bTMB had the similar distribution to tTMB. Among all the tumor and plasma samples we detected 8 gene mutations having a significant correlation with high TMB including BTG2, PIM1, DUSP2, HIST1H1E, BTG1, SOCS1, HIST1H1C, CD70 ( p< 0.05) . Table TMB distribution of different lymphoma subtypes Conclusions: Compared to other lymphoma subtypes, DLBCL had higher TMB. Particular gene mutation had correlation with high TMB.[Table: see text]