Clonal Evolution and Timing of Metastatic Colorectal Cancer

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where almost 50% of patients develop mostly liver metastasis during the course of the disease, with high mortality, despite improved management over recent years. Thus, elucidating the effects of therapy on metastatic CRC progression is essential. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naive and treated CRC primary tumours and metastases along with matched germline (n=30) from 30 patients. Somatic variants were analysed to define the genomic landscape during metastatic progression and assess the effect of therapy in metastatic CRC. This study provides deeper insights into the effect of treatment and mechanisms supporting liver-specific adaptation in metastatic CRC.