<p>Assessment of tumor mutation burden calculation from gene panel sequencing data</p>

Abstract

Background: High tumor mutation burden (TMB) is an emerging selection biomarker for immune checkpoint blockade in tumors such as melanoma and non-small cell lung cancer. TMB is typically calculated from whole genome sequencing or whole exome sequencing (WES) data. Recently, clinical trials showed that TMB can also be estimated from targeted sequencing of a panel of only a few hundred genes of interest, which can be performed at a high depth for clinical applications. Materials and methods: In this study, we systematically investigated the distribution of TMB and preferences at the gene and mutation level, as well as the correlation between TMB calculated by WES and panel sequencing data using somatic mutation data from 15 cancer types from The Cancer Genome Atlas (TCGA). Results: We proposed a pan-cancer TMB panel and demonstrated that it had a higher correlation with WES than other panels. Our panel could serve as a reference data-set for TMB-oriented panel design to identify patients for immunotherapy.

The mutational load and a T-cell inflamed tumor phenotype identify ovarian cancer patients rendering tumor-reactive T cells from PD-1+ tumor-infiltrating lymphocytes

“…The TMB values in our patients, as estimated using the TST170 panel, ranged from 3.8 to 24.8 mutations/Mb. These values were within the range of those found for OC using whole-exome sequencing [29] and FoundationOne [30], although the median values (8.6 mutations/Mb) were higher than those estimated with these methods (3-4 mutations/Mb) [29,30]. The use of a small gene panel and the low number of patients studied may have overestimated the median TMB values [31].…”

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

“…Chinese melanoma is mostly the mucosal type while malignant melanomas in Europe and the United States are mostly the skin type, the onset of which is usually the result of accumulation of genomic mutations caused by UV. Accordingly, previous studies have confirmed a higher TMB in skin type malignant melanoma [41,42]. A Chinese tumour patient study as well as a TCGA database study showed that gastric cancer and colorectal cancer also have relatively higher TMBs [41,43], but these studies have not fully demonstrated the impact of dMMR/MSI-H on TMB.…”

“…Accordingly, previous studies have confirmed a higher TMB in skin type malignant melanoma [41,42]. A Chinese tumour patient study as well as a TCGA database study showed that gastric cancer and colorectal cancer also have relatively higher TMBs [41,43], but these studies have not fully demonstrated the impact of dMMR/MSI-H on TMB. In order to provide more accurate information on TMB in different tumour types, our study specifically separated dMMR gastric and colorectal cancers from non-dMMR types Fig.…”

Comparison of commonly used solid tumor targeted gene sequencing panels for estimating tumor mutation burden shows analytical and prognostic concordance within the cancer genome atlas cohort

“…These findings have also been observed in an independent analysis of the TCGA data set. 28 Currently, gene panels are typically designed to identify actionable point mutations, indels or copy number variants and not to assess overall TMB. Further investigation may show that mutations in some genes are more readily tolerated than others because of functional redundancy, decreased neoantigen presentation due to loss of major histocompatibility complex (MHC) expression or combinations of other mechanisms.…”