Characterization of Korean Colorectal Cancer Reveals Novel Driver Gene and Clinically Relevant Mutations

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths worldwide, characterized by genomic heterogeneity arising from ethnic and interindividual differences. Producing region-specific data to characterize ethnic-specific somatic mutations is essential for advancing CRC research. Additionally, accurate somatic mutation detection requires paired tissue analyses to account for interindividual diversity. This study aims to highlight the importance of ethnic diversity in shaping CRC's genomic landscape and emphasize the necessity for region-specific data to refine diagnostic and therapeutic approaches. This study emphasizes the need for region-specific data by analyzing an unprecedented 197 paired samples from the Korean CRC cohort through whole-genome sequencing. We identified 78 potential driver genes. Notably, <i>CBWD5</i>, <i>LRRIQ3</i>, <i>TRIM64B</i>, <i>SPINK5</i>, and <i>ZNRF2</i> were linked to recurrence, presenting potential therapeutic targets. Our analysis revealed 30 mutational hotspots, with significant variants in <i>KRAS</i> (25%, G12A, G12D, G12V), <i>MAP1A</i> (12%, V2300G), and <i>TP53</i> (8%, R175H). We identified a significant co-occurrence between <i>KRAS</i> 12 mutation and <i>PIK3CA</i> 545 mutation. Our findings demonstrate potential driver genes and mutational hotspots associated with CRC patient, characterizing the mutational landscape related to clinical characteristics. Significantly advancing our understanding of CRC's heterogeneous nature, this study lays a solid foundation for devising more efficacious management strategies.