Abstract C016: Computational analysis of missense mutations & amino acid substitution pattern of 12 selective cancers’ candidate genes using TCGA datasets

Abstract The Cancer Genome Atlas (TCGA) has made it possible to study cancer-related mutations, including missense mutations. We used the PolyPhen scoring system to determine the functional impact of missense mutations. Mutation data of genes from 12 selective cancers (Head & Neck Squamous Cell Carcinoma, Kidney Chromophobe, Liver Heptocellular Carcinoma, Kidney Renal Clear Cell Carcinoma, Kidney Renal Papillary Cell Carcinoma, Lung Squamous Cell Carcinoma, Prostate Adenocarcinoma, Thyroid Carcinoma, Bladder Urothelial Carcinoma, Lung Adenocarcinoma, Breast Invasive Carcinoma, Stomach Adenocarcinoma) were downloaded from the cBioPortal; subsequently, the missense mutations that met these two criteria: 1. number of mutations in the sample must be greater than or equal to 5; 2. functional impact must be possibly or probably damaging based upon PolyPhen score, were identified. We found that Papillary Renal Cell Carcinoma had the highest average PolyPhen score of 0.932 while Prostate Adenocarcinoma had the lowest average PolyPhen score of 0.896; showing that the missense mutations in Papillary Renal Cell Carcinoma had more detrimental missense mutations. Further analysis showed that amino acid Arginine (R) was the most commonly substituted amino acid among the 12 cancers we studied. The 5 relatively high substituted amino acids were R (15.8%), E (9.33%), D (9.0%), G (8.94%), S (8.48%). In addition, we also studied the disparities of most commonly substituted amino acids in White, Black, and Asian. We found that in the Black race, the most common substitution percentages were amino acids R (20.73%), G (18.52%), E (16.05%), D (12.11%), S (11.75%). In the White race, the most common substitution percentages were amino acids R (16.36%), G (9.03%), D (9.01%), E (8.81%), S (8.56%). In the Asian race, the most common substitution percentages were amino acids I (34.91%), E (24.32%), R (18.46%), T (16.45%), P (15.27%). This interesting finding demonstrated that the White and the Black races shared more similarity of the mutation pattern in the most frequently substituted amino acids. In contrast, the Asian race had a distinct amino acid substitution pattern of missense mutations. By examining the mutation pattern, we hope to identify key genes as biomarkers so that the somatic mutation landscape of different races can be described. Citation Format: Lucas C. Wang, Kai He, Allen Bai. Computational analysis of missense mutations & amino acid substitution pattern of 12 selective cancers’ candidate genes using TCGA datasets [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C016.