Systematic Analysis of Somatic Mutations Driving Cancer: Uncovering Functional Protein Regions in Disease Development

The study introduced a novel method called iSiMPRe to identify significantly mutated protein regions (SiMPRes) in cancer-related genes by analyzing somatic mutations. By examining data from various cancer genome projects, the researchers identified approximately 500 protein regions associated with 27 cancer types, including both known and novel cancer genes. iSiMPRe was particularly effective in recognizing oncogenes and tumor suppressor genes, outperforming other methods like OncoDriveClust and eDriver. The method highlighted the clustering of mutations in specific protein regions, emphasizing their role in tumorigenesis and potential as drug targets. While iSiMPRe successfully identified many cancer genes, it was less effective for genes primarily altered by chromosomal translocations or truncating mutations, suggesting the need for a combined approach for comprehensive cancer driver gene identification.