Impact of Liver Cancer Somatic Mutations on Protein Structures and Functions

Background: Cancers result due to the dysregulation of gene expression. They can be identified on the basis of driver mutations and genetic signatures. Proteins are macromolecules that regulate the structure and function of body organs. Missense somatic mutations play a critical role in the development of cancer by altering the underlying properties of corresponding proteins. The extent to which the chemical properties and composition of amino acid are changed in cancer is still under investigation. Objective: The main objective of this study is to identify amino acid changes that might be responsible for causing liver cancer. It also aims to identify frequently mutated genes associated with liver cancer. Methods: The mutation data of Hepatocellular Carcinoma (HCC) in coding variants was retrieved from COSMIC (Catalogue of Somatic Mutations in Cancer) databases. Different bioinformatics tools were used to study genetic alterations at the protein level. The identified amino acid replacements were compared with Grantham’s distance to determine similarity/ dissimilarity between substituted amino acids. Results: The results show that TP53, CTNNB1, MUC16, PCLO, and TTN genes were frequently mutated in liver cancer. This study also reveals that the non-synonymous mutations, in analyzed dataset, cause loss of Alanine. Conclusion: The amino acid replacements, identified in this study, may act as signatures for early diagnosis of liver cancer. They may also be helpful in understanding the development of liver cancer.