Genomic trajectories of colorectal cancer with choroidal metastasis: longitudinal insights from tissue and liquid biopsy via next-generation sequencing.

Colorectal cancer (CRC) is a leading cause of cancer-related death, with metastasis commonly involving the liver, lungs, and peritoneum. Ocular dissemination, particularly to the choroid, is exceedingly rare. Here, we present a case of metastatic CRC with choroidal involvement, characterized through longitudinal genomic profiling using the TruSight Oncology 500 (TSO500) assay on both tumor tissue and circulating tumor DNA (ctDNA). A 66-year-old male with metastatic CRC initially demonstrated RAS/BRAF wild-type status, microsatellite stability (MSS), and a moderate tumor mutational burden (TMB: 7.1 mut/Mb). Upon developing visual symptoms and radiologically confirmed choroidal metastasis, ctDNA analysis revealed significant clonal evolution, including new Tier IA alterations (EGFR amplification and JAK2 p.V617F mutation) absent in the primary tumor. The ctDNA profile showed a hypermutated phenotype (TMB: 44.9 mut/Mb), suggesting selection of aggressive subclones under treatment pressure. This is the first report to integrate tissue- and liquid-based NGS in a CRC patient with ocular metastasis, highlighting the dynamic nature of tumor evolution and the utility of liquid biopsy in identifying emerging, clinically relevant mutations. The acquisition of EGFR amplification may indicate resistance to anti-EGFR therapy and organ-specific tropism, while the JAK2 mutation suggests potential involvement in immune escape and niche adaptation. These findings underscore the importance of comprehensive genomic surveillance in metastatic CRC and provide novel insights into the biology of choroidal dissemination.