Molecular Characterization of Ovarian Metastases from Colorectal Cancer Using Circulating Tumor DNA Analysis.

INTRODUCTION: Ovarian metastases from colorectal cancer (CRC) are uncommon but are associated with poor prognosis and therapeutic challenges. These lesions may exhibit discordant responses to systemic therapy, suggesting site-specific biological heterogeneity. However, the molecular characteristics of CRC-associated ovarian metastases remain insufficiently defined. We aimed to characterize the circulating tumor deoxyribonucleic acid (ctDNA) landscape of ovarian metastatic CRC using a plasma-based deep sequencing approach. METHODS: Plasma samples from patients with CRC and ovarian metastases were analyzed using cancer personalized profiling by deep sequencing. Pathogenic mutations and copy-number alterations were identified to delineate the genomic features of this metastatic subset. RESULTS: Pathogenic genomic alterations were detected in the majority of patients. Canonical CRC driver mutations, including TP53, KRAS, and APC, were observed at frequencies comparable to those reported in large-scale genomic datasets such as The Cancer Genome Atlas. In addition, recurrent amplification of growth factor receptor genes, including EGFR, MET, and ERBB2, was identified. Detectable tumor-derived alterations in plasma indicate active ctDNA shedding from ovarian lesions, supporting the feasibility of noninvasive genomic profiling in this setting. CONCLUSIONS: CRC-associated ovarian metastases retain the core genomic architecture of colorectal tumorigenesis while demonstrating recurrent receptor tyrosine kinase amplifications that may reflect adaptive clonal evolution within the ovarian microenvironment. Plasma-based ctDNA profiling provides a feasible approach for molecular characterization of this rare metastatic phenotype and may contribute to improved understanding of site-specific tumor biology.