Genomic landscape of colorectal carcinogenesis

Purpose The molecular pathogenesis of solid tumour was first assessed in colorectal cancer (CRC). To date, <= 100 genes with somatic alterations have been found to inter-connectively promote neoplastic transformation through specific pathways. The process of colorectal carcinogenesis via genome landscape is reviewed on the basis of an adenoma-to-carcinoma sequence, as shown by serial histological and epidemiological observations. Methods The relevant literatures from PubMed (1980-2021) have been reviewed for this article. Results The major routes of CRC development, chromosomal instability (CIN), microsatellite instability (MSI), and the serrated route either via CIN or MSI, proceed through the respective molecular pathway of colorectal carcinogenesis. Particular aspects of CRC carcinogenesis can also be determined by evaluating familial CRCs (FCRC) and genotype-phenotype correlations. Specific causative gene alterations still leave to be identified in several FCRCs. Otherwise, recently verified FCRC can be particularly notable, for example, EPCAM-associated Lynch syndrome, polymerase proofreading-associated polyposis, RNF43-associated polyposis syndrome or NTHL1 tumour syndrome, and hereditary mixed polyposis syndrome. The oncogenic landscape is described, including representative pathway genes, the three routes of carcinogenesis, familial CRCs, genotype-phenotype correlations, the identification of causative genes, and consensus molecular subtypes (CMS). Conclusion Whole genome research using multi-gene panels (MGPs) has facilitated high through-put detection of previously unidentified genes involved in colorectal carcinogenesis. New approaches designed to identify rare variants are recommended to consider their alterations implicated in the molecular pathogenesis.

Automated summary

This study assessed the molecular pathogenesis of solid tumors, focusing specifically on colorectal cancer. Through a review of relevant literature, it was found that colorectal carcinogenesis mainly occurs through chromosomal instability, microsatellite instability, and serrated pathway. Familial colorectal cancers and genotype-phenotype correlations also play a role in colorectal carcinogenesis. The use of multi-gene panels has facilitated the detection of previously unidentified genes involved in colorectal carcinogenesis.