Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1288-1301
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1288
Molecular testing for colorectal cancer: Clinical applications
Evgeny Imyanitov, Ekaterina Kuligina
Evgeny Imyanitov, Ekaterina Kuligina, Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia
Evgeny Imyanitov, Department of Medical Genetics, St.-Petersburg Pediatric Medical University, Saint-Petersburg 194100, Russia
Evgeny Imyanitov, Department of Oncology, I.I. Mechnikov North-Western Medical University, Saint-Petersburg 191015, Russia
Author contributions: Imyanitov E wrote the article draft; Kuligina E prepared the illustration; Both authors reviewed the literature data, edited and approved the final version of the manuscript.
Supported by Ministry of Science and Higher Education of the Russian Federation, No. 075-15-2020-789.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Evgeny Imyanitov, DSc, Professor, Department of Tumor Biology, N.N. Petrov Institute of Oncology, Pesochny, St.-Petersburg 197758, Russia.
Received: February 21, 2021
Peer-review started: February 21, 2021
First decision: June 16, 2021
Revised: June 19, 2021
Accepted: August 24, 2021
Article in press: August 24, 2021
Published online: October 15, 2021

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.

Keywords: Colorectal cancer, Anti-epidermal growth factor receptor therapy, KRAS, NRAS, BRAF, HER2, Microsatellite instability, MUTYH, Hereditary cancer

Core Tip: Molecular genetic analysis is an integral component of colorectal cancer (CRC) management. Comprehensive KRAS and NRAS testing is mandatory for selection of patients for anti-epidermal growth factor receptor (EGFR) therapy. BRAF V600E mutated cancers are responsive to combination of BRAF and EGFR inhibitors. CRCs with HER2 amplification and overexpression can be controlled by the down-regulation of this receptor. Immune therapy is highly effective in CRCs with exceptionally high tumor mutation burden, e.g., in cancers with microsatellite instability, MUTYH gene inactivation or mutations in the POLE gene. CRC patients with early disease onset, specific tumor features or family history of the disease require germ-line DNA testing.