Impact of Chemotherapy Exposure and DNMT3A Variants on Tumor Mutation Burden in Advanced Colorectal Cancer

Background This study aimed to analyze the impact of clinical and environmental factors and individual genetic variants on tumor mutation burden (TMB) in cases of advanced or recurrent colorectal cancer (CRC) for which comprehensive genomic profiling (CGP) was performed. Methods Fifty patients with advanced or recurrent CRC for whom CGP was conducted were included in this study. Data extraction was performed from extensible markup language (XML) files of the test data. Reference cases were selected from 1,133 CRC cases registered in the public Memorial Sloan Kettering (MSK) dataset, CRC_MSK_2017, on cBioPortal. Analyses conducted included OncoPrint, correlation, and single nucleotide variant (SNV) analysis. Furthermore, factors associated with TMB were identified through an analysis of the relationships between TMB and clinicopathological factors, environmental factors, and genetic variants in individual cases. Results The three most common genes in which variants were observed were consistent with those in the public dataset, although their frequencies were higher. The next most common genes with variants differed from those in the public dataset, and differences in peak variants were observed for APC and TP53 . The number of treatment regimens was significantly associated with TMB, and cases with DNMT3A gene variants had significantly higher TMB. Conclusion CGP in CRC in the present study indicated the potential for racial and geographic differences in DNA variant frequencies, and associations between the number of treatment regimens and presence of DNMT3A variants and TMB.