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

person Hui Zhou Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China info_outline Hui Zhou, Xinhua Du, Tingting Zhao, Zhou Ouyang, Wei Liu, Mingyang Deng, Qian He, Yuting Yi, Lian Dai, Ling Yang, Xuefeng Xia

Authors person Hui Zhou Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China info_outline Hui Zhou, Xinhua Du, Tingting Zhao, Zhou Ouyang, Wei Liu, Mingyang Deng, Qian He, Yuting Yi, Lian Dai, Ling Yang, Xuefeng Xia Organizations Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, Geneplus-Beijing Institute, Beijing, China, Xiangya Hospital Central South University, Changsha, China, The Second Xiangya Hospital of Central South University, Changsha, China, Hunan Cancer Hospital the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, Shangcha, China, Geneplus-Beijing, Beijing, China, Houston Methodist Research Institute, Weill Cornell School of Medicine, Houston, TX Abstract Disclosures Research Funding Pharmaceutical/Biotech Company 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. Lymphoma subtypes TMB-H ratio Median(25% Percentile-75% Percentile) tumor plasma tTMB bTMB DLBCL 34.09% (45/132) 34.25% (25/73) 8.85 (5.10-14.60) 10.03 (5.61-14.46) Small B cell lymphoma 3.70% (1/27) 0% (0/15) 3.54 (2.36-4.72) 3.15 (1.18-7.08) Peripheral T-cell lymphoma 3.85% (1/26) 16.67% (1/6) 2.36 (1.18-4.28) 2.11 (0.62-5.96) NK/T cell lymphoma 0% (0/3) 0% (0/4) 5.90 (4.72-8.80) 3.15 (1.10-4.93)