Chinese pan‐cancer patient genomic characteristics: A comprehensive analysis based on the National Cancer Center–Clinical Diagnostics Knowledgebase real‐world clinical sequencing cohort

Abstract Precision oncology strategies guided by tumor molecular profiling often target key genomic aberrations in patients. Herein, we assembled National Cancer Center–Clinical Diagnostics Knowledgebase, compiling clinical targeted sequencing data from 6935 tumor tissues and matched normal samples, along with available pathological and clinical information. Comprehensive genomic profiling was conducted to characterize tumor type‐specific somatic alterations, and comparative analyses were performed across distinct cohorts. Key genomic characteristics included high‐frequency alterations in TP53 (57.8%), APC (22.6%), KRAS (21.3%), and EGFR (17.5%), among which EGFR mutations were significantly enriched in lung adenocarcinoma patients. In this cohort, 70.2% of the samples harbored at least one clinically actionable genomic aberration. 14.9% of patients showed high tumor mutational burden (TMB > 10 mutations/Mb), and the TMB level was significantly higher in patients with microsatellite instability‐high than in those with microsatellite stability. We also correlated next‐generation sequencing (NGS) results with conventional molecular pathology assays. We found high consistency between ERBB2 focal amplification cases determined by NGS and clinically targetable ERBB2 amplification/HER2 overexpression cases. In conclusion, this study constructed a large‐scale real‐world genomic dataset representative of Chinese cancer patients, spanning multiple tumor types. Moreover, our findings underscore the clinical value of NGS in identifying patients with ERBB2 amplification who may potentially benefit from targeted treatments, particularly in non‐small‐cell lung cancer cases where NGS panel testing is prioritized.