An effective and accurate algorithm for measuring the tumor mutation burden of cancer patients plasma.

Abstract

e14177 Background: Tumor Mutation Burden (TMB) is deemed to be one of the effective genomic biomarkers that are used to predict the response to PD-1/PD-L1 blockade immunotherapy. As an exciting biomarker for diagnose and an alternative assess method for tissue TMB (tTMB), blood TMB (bTMB) is measured to further distinguish the patients who may benefit from immunotherapy. However, there is no recognized rule to calculate bTMB so far. Methods: In this study, we developed an in-house algorithm called PTAB to calculate bTMB of plasma, all credible single nucleotide variants and insertion-deletions whose allele frequency is greater than 1% are selected in PTAB without synonymous mutations and drive mutations. We also constructed a 636 genes panel which region size is 1.95Mb to identify all the associated mutations, due to the high costs and long turnaround time of WES. Results: Meanwhile, we assessed a cohort of 50 lung cancer plasma samples and paired tissues to ensure the consistency of different algorithm used for tissue and plasma. The results show that Pearson correlation coefficient (R2) between bTMB and tTMB in 50 patients is 0.7128. In addition, we found that the consistency of lung squamous carcinomas obviously higher than that of lung adenocarcinoma (0.8932 vs. 0.5947). We also described the distribution of bTMB and tTMB value of Chinese patients, including 594 tissue samples and 561 plasma samples from 8 types of cancers, including lung cancer, colorectal cancer, breast cancer, et al. The overall comparative analysis of 1155 previous data suggested that the distribution modes of bTMB and tTMB were almost same in certain cancer type, though the level of bTMB was generally lower than that of tTMB. Conclusions: Preliminary data highlight that PTAB is an effective and accurate algorithm for measure the TMB of plasma. The applicability of bTMB testing on liquid biopsy needs further investigation and may be clarified within the ongoing clinical trials.