MULTIGENE TESTINGIN GENETIC SCREENING OF HEREDITARYAND SPORADIC COLORECTAL CANCER:A LITERATURE REVIEW

Abstract

Relevance: Molecular genetic testing to determine the patient's genotype and tumor molecular profile 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 across colorectal cancer (CRC) diagnostics and therapy, where genetic components make a significant contribution. Currently, practical oncology requires a review of high-throughput sequencing systems for the genetic screening of hereditary and sporadic CRC variants and for the optimization of 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 70 original research and review articles available in open-access databases, including Google Scholar, Web of Science, Springer Link, Scopus, ScienceDirect, PubMed, and BMJ. 

Results: NGS-based multigene testing enables the simultaneous analysis of multiple genes involved in carcinogenesis, the identification of germline pathogenic mutations associated with hereditary tumor syndromes, and the detection of genetic variants in less-studied regions of genes, such as introns and untranslated regions, which help 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 approximately 25% of CRC cases are familial, fewer than 5% of families are studied genetically. The analyzed data confirm the need to transition from phenotypic panels to comprehensive panels, encompassing all identified genes involved in hereditary tumor syndromes or whole-genome sequencing. In addition, identifying new variants with moderate and low penetrance, as well as those with uncertain functional significance, expands the phenotypic spectrum of CRC and necessitates further studies to determine their inclusion in diagnostic sequencing panels.