Genomic Alterations and Clinical Characterization in Chinese Patients with Metastatic Colorectal Cancer.

BACKGROUND

Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as , , and microsatellite instability (MSI). Novel genomic changes, including amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies.

METHODS

A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated.

RESULTS

The cohort's genomic profiling revealed mutations in 78%, in 60%, and in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. / amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except ) that could be targeted therapeutically. The (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a mutation. Notably, survival analysis showed no significant differences in OS between mutant loci and mutations ( = 0.436). However, mutations were associated with a poorer prognosis than wild-type and non- mutations (16.3 months vs. 29.5 and 31.1 months, respectively; < 0.001).

CONCLUSIONS

This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.