OTDOncology Treatment Discovery3083-49962981-8079Bio-Byword Scientific Publishing Pty. Ltd.10.26689/OTD.v4i3.15984ArticleMutational Landscape and Clinicopathological Correlates of 553 Chinese Colorectal Cancer Cases Assessed by 116-Gene Targeted Sequencinghttps://artdesignp.com/journal/OTD/4/3/10.26689/OTD.v4i3.15984LiuYitong,LiJianglin,WuMingfeng,LuoZidan,SunYiyun,ChenXinyu,ZhouEnle2026432026-10-20Objective: 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.Colorectal neoplasms, Targeted sequencing, Mutational landscape, Copy number amplification, Gene fusion, Molecular stratification

[1]   Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3): 209–249. [2]   Cancer Genome Atlas Network, 2012, Comprehensive Molecular Characterization of Human Colon and Rectal Cancer. Nature, 487(7407): 330–337. [3]   Chen W, Zheng R, Baade PD, et al., 2016, Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 66(2): 115–132. [4]   Zhao Q, Wang F, Chen YX, et al., 2022, Comprehensive Profiling of 1015 Patients’ Exomes Reveals Genomic-Clinical Associations in Colorectal Cancer. Nature Communications, 13: 2342. [5]   Guo L, Wang Y, Yang W, et al., 2023, Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis. Gastroenterology, 165(2): 414–428. [6]   Cheng B, Xu L, Zhang Y, et al., 2024, Correlation Between NGS Panel-Based Mutation Results and Clinical Information in Colorectal Cancer Patients. Heliyon, 10(7): e29299. [7]   Li MM, Datto M, Duncavage EJ, et al., 2017, Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists. Journal of Molecular Diagnostics, 19(1): 4–23. [8]   Richards S, Aziz N, Bale S, et al., 2015, Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5): 405–424. [9]   Tate JG, Bamford S, Jubb HC, et al., 2019, COSMIC: The Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Research, 47(D1): D941–D947. [10] Cerami E, Gao J, Dogrusoz U, et al., 2012, The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data. Cancer Discovery, 2(5): 401–404. [11] National Comprehensive Cancer Network, 2025, NCCN Clinical Practice Guidelines in Oncology: Colon Cancer (Version 3.2025), visited on July 20, 2026, https://www.nccn.org. [12] Sartore-Bianchi A, Trusolino L, Martino C, et al., 2016, Dual-Targeted Therapy With Trastuzumab and Lapatinib in Treatment-Refractory, KRAS Codon 12/13 Wild-Type, HER2-Positive Metastatic Colorectal Cancer (HERACLES): A Proof-of-Concept, Multicentre, Open-Label, Phase 2 Trial. The Lancet Oncology, 17(6): 738–746. [13] Blank A, Schenk L, Moch H, 2021, The Impact of MYC Alterations in Colorectal Cancer. Der Pathologe, 42(3): 255–261. [14] Drilon A, Laetsch TW, Kummar S, et al., 2018, Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. New England Journal of Medicine, 378(8): 731–739. [15] Lin JJ, Riely GJ, Shaw AT, 2019, Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discovery, 9(7): 899–915. [16] Subbiah V, Gainor JF, Rahal R, et al., 2018, Precision Targeted Therapy With BLU-667 for RET Fusion-Positive Solid Tumors. Cancer Discovery, 8(7): 836–849. [17] Fearon ER, Vogelstein B, 1990, A Genetic Model for Colorectal Tumorigenesis. Cell, 61(5): 759–767. [18] Yaeger R, Chatila WK, Lipsyc MD, et al., 2018, Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer. Cancer Cell, 33(1): 125–136. [19] Andre T, Shiu KK, Kim TW, et al., 2020, Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. New England Journal of Medicine, 383(23): 2207–2218. [20] Overman MJ, Lonardi S, Wong KYM, et al., 2018, Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. Journal of Clinical Oncology, 36(8): 773–779. [21] Cercek A, Lumish M, Sinopoli J, et al., 2022, PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. New England Journal of Medicine, 386(25): 2363–2376. [22] Kopetz S, Grothey A, Yaeger R, et al., 2019, Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. New England Journal of Medicine, 381(17): 1632–1643. [23] Fakih MG, Kopetz S, Kuboki Y, et al., 2022, Sotorasib for Previously Treated Colorectal Cancers With KRAS G12C Mutation (CodeBreaK100): A Prespecified Analysis of a Single-Arm, Phase 2 Trial. The Lancet Oncology, 23(1): 115–124. [24] Strickler JH, Cercek A, Siena S, et al., 2023, Tucatinib Plus Trastuzumab for Chemotherapy-Refractory, HER2-Positive, RAS Wild-Type Unresectable or Metastatic Colorectal Cancer (MOUNTAINEER): A Multicentre, Open-Label, Phase 2 Study. The Lancet Oncology, 24(5): 496–508. [25] Yaeger R, Corcoran RB, 2019, Targeting Alterations in the RAF-MEK Pathway. Cancer Discovery, 9(3): 329–341. [26] Palles C, Cazier JB, Howarth KM, et al., 2013, Germline Mutations Affecting the Proofreading Domains of POLE and POLD1 Predispose to Colorectal Adenomas and Carcinomas. Nature Genetics, 45(2): 136–144.