Molecular testing for colorectal cancer: Clinical applications

Molecular genetic analysis is an integral part of colorectal cancer (CRC) management. The choice of systemic therapy for CRC is largely based on the results of tumor molecular testing. Evaluation of the KRAS and NRAS gene status is mandatory for consideration of anti-epidermal growth factor receptor (EGFR) therapy. Tumors with the BRAF V600E substitution are characterized by aggressive behaviour, may require intensified cytotoxic regimens and benefit from combined BRAF and EGFR inhibition. The inactivation of DNA mismatch repair (MMR), or MUTYH gene, or DNA polymerase epsilon results in excessive tumor mutational burden; these CRCs are highly antigenic and therefore sensitive to immune checkpoint inhibitors. Some CRCs are characterized by overexpression of the HER2 oncogene and respond to the appropriate targeted therapy. There are CRCs with clinical signs of hereditary predisposition to this disease, which require germline genetic testing. Liquid biopsy is an emerging technology that has the potential to assist CRC screening, control the efficacy of surgical intervention and guide disease monitoring. The landscape of CRC molecular diagnosis is currently undergoing profound changes due to the increasing use of next generation sequencing.