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

## TL;DR

This study uses whole-genome sequencing of 197 Korean colorectal cancer samples to identify new driver genes and mutations linked to cancer recurrence and treatment response.

## Contribution

The study identifies novel driver genes and clinically relevant mutations specific to Korean colorectal cancer patients.

## Key findings

- Identified 78 potential driver genes, including CBWD5, LRRIQ3, TRIM64B, SPINK5, and ZNRF2 linked to recurrence.
- Discovered 30 mutational hotspots, with significant variants in KRAS, MAP1A, and TP53.
- Found a significant co-occurrence between KRAS 12 and PIK3CA 545 mutations.

## Abstract

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, CBWD5, LRRIQ3, TRIM64B, SPINK5, and ZNRF2 were linked to recurrence, presenting potential therapeutic targets. Our analysis revealed 30 mutational hotspots, with significant variants in KRAS (25%, G12A, G12D, G12V), MAP1A (12%, V2300G), and TP53 (8%, R175H). We identified a significant co‐occurrence between KRAS 12 mutation and PIK3CA 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.

This study utilizes whole‐genome sequencing of 197 paired samples to conduct mutational profiling of colorectal cancer (CRC) in Korean patients, identifying novel driver genes associated with recurrence. The research provides insights into oncogenic pathways and highlights clinically significant variants, emphasizing the importance of ethnic diversity in CRC patient stratification.