Identification of clinicopathological‐specific driver gene and genetic subtyping of colorectal cancer

• DOI: 10.1111/cas.16432
• Publication Date: 2025-01-11T10:33:21Z
• Authors: Jianjiong Li; Chunnian Wang; Changshun Yang; Hua Bao; Ningyou Li; Xianqiang Huang; Wei Gong; Xinyue Hong; Jiani C. Yin; Jiaohui Pang; Meifu Gan; Danping Yuan
• Keywords: Subtyping; ERBB4; Microsatellite Instability

Abstract This study analyzed targeted sequencing data from 6530 tissue samples patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup‐specific driver genes, using three algorithms for overall CRC as well across different clinicopathological subgroups. We 425 cancer‐related identifying 101 potential including 36 novel CRC. Notably, some genes demonstrated subgroup specificity; instance, ERBB4 was found a male‐specific gene mutations of only influenced the prognosis male sex disparity validated in an independent large‐scale Memorial Sloan Kettering Cancer Center cohort 2444 samples. Furthermore, network‐based stratification based on protein–protein interaction, we classified microsatellite stable (MSS) unstable (MSI) CRCs into six major subtypes, respectively, each showing unique phenotypes prognoses. In MSS CRC, cluster 5 (APCAMER1–KRAS) 2 (RNF43–BRAF–PIK3CA) were predominant, showed superior survival compared 2. extensive heterogeneity underscores complexity suggests significant implications treatment prognostic assessments.