Volume 4,Issue 3
Mutational Landscape and Clinicopathological Correlates of 553 Chinese Colorectal Cancer Cases Assessed by 116-Gene Targeted Sequencing
Objective: Comprehensive molecular profiling of colorectal cancer (CRC) can inform precision oncology, yet real-world data from Chinese cohorts based on clinical targeted panels remain limited. This study aimed to characterize the mutational landscape of Chinese CRC using a 116-gene targeted next-generation sequencing (NGS) panel and to evaluate associations between key genomic alterations and clinicopathological features. Method: We retrospectively enrolled 553 patients with pathologically confirmed colorectal adenocarcinoma or its histological subtypes who underwent 116-gene targeted sequencing. Single-nucleotide variants (SNV)/short insertions and deletions (InDel), copy number amplifications, and gene fusions were identified using a standardized bioinformatics pipeline. Somatic variants were annotated using both AMP/ASCO/CAP oncogenicity labels and laboratory ACMG-style pathogenicity labels. Gene-level analyses were based on a nonsynonymous variant set. Associations with clinicopathological features were assessed using Fisher’s exact test with Benjamini-Hochberg correction. Potentially actionable molecular events were stratified into three evidence-based tiers. Results: Among 553 CRC patients, 343 (62.0%) were male and 210 (38.0%) were female, with a median age of 62 years (range, 17-94 years). The rectum was the most common tumor site (53.3%), followed by the left colon (24.8%) and right colon (21.9%). A total of 4,725 SNV/InDel variants were identified, of which 3,107 were nonsynonymous (involving 102 genes); the median number of nonsynonymous mutations per patient was 4 (range, 1-60). The five most frequently mutated genes were TP53 (78.1%), KRAS (53.0%), APC (49.4%), PIK3CA (22.4%), and FBXW7 (20.6%). Copy number amplification was detected in 12.7% of patients (70/553), most commonly involving MYC (2.9%) and FGFR3 (2.5%). Gene fusions were identified in 7 patients (1.3%). Co-mutation analysis revealed significant co-occurrence of TP53 and APC (OR = 2.07, 95% CI: 1.36-3.14, adjusted p = 0.005) and mutual exclusivity between KRAS and BRAF (OR = 0.10, 95% CI: 0.04-0.25, adjusted p < 0.001). By evidence-based tiering, 19.9% (110/553) of patients harbored at least one Tier 1 molecular event, and 66.7% (369/553) harbored at least one Tier 1 or Tier 2 event. Conclusion: This study delineates the 116-gene mutational landscape of 553 Chinese CRC patients, characterizing the TP53-KRAS-APC core mutation pattern, hotspot distributions, low-frequency copy number amplifications and fusion events, and a tiered map of potentially actionable molecular events, providing real-world regional data to inform precision oncology in CRC.
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