Multigene testing in genetic screening of hereditary and sporadic colorectal cancer: A literature review

Abstract

Relevance: Molecular genetic testing to determine the patient's genotype and molecular profile of the tumor is a key component of a personalized approach to treatment and follow-up. Current research in genetic screening focuses on transitioning from phenotypic diagnostic panels and PCR testing of predisposition genes to large panels that include many identified genes or whole-genome sequencing. Multigene testing is widely used in various areas of colorectal cancer (CRC) diagnostics and therapy, in which genetic components make a significant contribution. Currently, practical oncology requires a review of high-throughput sequencing systems for genetic screening of hereditary and sporadic variants of CRC and optimization of its early diagnosis in relatives of patients.

The study aimed to review the methodology and current results of next-generation sequencing (NGS) applications for genetic screening of hereditary and sporadic colorectal cancer.

Methods: This analytical review included 114 original research and review articles available in open access in Google Scholar, Web of Science, Springer Link, Scopus, Science Direct, PubMed, and BMJ databases.

Results: NGS-based multigene testing enables the simultaneous analysis of multiple genes involved in carcinogenesis, identification of germline pathogenic mutations associated with hereditary tumor syndromes, as well as genetic variants in less studied areas of genes, such as intronic and untranslated regions, which helps to identify previously unknown factors predisposing to colorectal cancer.

Conclusion: Molecular genetic diagnostics facilitate personalized treatment of patients and individualized clinical examination of relatives from risk groups. However, although about 25% of CRC cases are familial, about 95% of families are not genetically studied. The analyzed data confirm the need to move from phenotypic panels to large panels, including all identified genes involved in hereditary tumor syndromes or whole genome sequencing. In addition, identifying new variants with moderate and low penetrance or variants with uncertain functional significance expands the phenotypic spectrum of CRC and necessitates further studies of these variants for inclusion in diagnostic sequencing panels.