Pan-cancer analysis of heterogeneity of tumor mutational burden and genomic mutation under treatment pressure

作者：Rui Huang, Yen-Lin Huang, Na An, Jiajia Hu, Chenyan Wu, Yuxuan Chen, Jiayi Chen, Qingqing Zhao, Rui‐Hua Xu, Sitong Yuan, F. Wang · 发表于：ESMO Open · 年份：2024 · DOI：10.1016/j.esmoop.2024.103494 · 被引用次数：13 · 研究领域：Cancer Immunotherapy and Biomarkers、Multiple and Secondary Primary Cancers、Immunotherapy and Immune Responses

BACKGROUND: High tumor mutational burden (TMB) is one of the widely researched predictive biomarkers of immune checkpoint inhibitors and has been shown to be closely related with response to immunotherapy in multiple cancer types. However, for patients who have failed conventional therapy and are about to undergo immunotherapy, there is no consensus recommendation on the timing of tumor sampling for TMB analysis, and the effects of different therapies on TMB have not been clarified. This retrospective observational study aimed to investigate the heterogeneity of TMB and genomic mutation under the treatment pressure. PATIENTS AND METHODS: We retrospectively collected the available genomic and therapeutic information from 8051 samples across 15 tumor types (>50 samples/tumor) found in 30 published studies and investigated the distribution and heterogeneity of TMB under treatment across diverse cohorts. RESULTS: This integrated analysis has shown anticancer treatments increased TMB. Significant effects of treatment on TMB were more frequently observed in tumor types with lower treatment-naïve TMB, including breast, prostate, and pediatric cancers. For different cancer therapies, chemotherapy was prone to be correlated with an increased TMB in most cancer types. Meanwhile, the fraction of the TMB-high category of breast, prostate, and bladder cancers and glioma increased significantly after chemotherapy. Several actionable genes including ERS1 and NF1 in breast cancer, as well as...