Next‐Generation Sequencing‐Based Analysis of the Genetic Mutation Spectrum in Colorectal Cancer: A Large Single‑Center Study From Southeast China With Cross‑Population Comparison

test. Sequencing analysis revealed that 12 patients harbored no detectable mutations in the targeted genes. Among the remaining 369 patients, somatic variants were identified across 30 genes. Regarding mutational patterns, 115 cases (30.2%) exhibited single-gene mutations, 158 cases (41.5%) showed two co-occurring mutations, and 96 cases (25.2%) carried alterations in three or more genes. The most frequently mutated genes were TP53 (76.9%), KRAS (47.8%), and PIK3CA (18.9%). TP53 mutations were significantly enriched in left-sided colon cancers (p < 0.0001). In contrast, both KRAS (p = 0.010) and PIK3CA (p = 0.001) mutations were significantly associated with right-sided colon cancers. Furthermore, the frequency of PIK3CA mutations was significantly higher in MSI-high tumors compared to MSS tumors. This study demonstrates significant associations between specific gene mutations and distinct clinicopathological characteristics. The findings underscore the importance of integrating molecular profiling with conventional clinicopathological parameters for precise stratification.