Genomic diversity and <i>BCL9L</i> mutational status in CTC pools predict overall survival in metastatic colorectal cancer

Abstract The genomic diversity of circulating tumor cells (CTCs) and its clinical implications remain poorly understood. In this study, we characterized the mutational landscape of CTC pools stemming from 29 metastatic colorectal cancer (mCRC) patients and examined its relationship with disease progression. Our analysis revealed substantial variation in mutational burden among patients, with all CTC pools harboring non-silent mutations in key CRC driver genes. Importantly, higher genomic diversity in CTC pools was significantly associated with reduced overall survival. Furthermore, non-silent mutations in BCL9L emerged as a strong predictor of patient survival. Taken together, these findings underscore the potential of CTC genomic profiling as a promising prognostic tool in mCRC and highlight the need for further research into its clinical applications.