Genomic landscape of colorectal carcinogenesis

J Cancer Res Clin Oncol. 2022 Mar;148(3):533-545. doi: 10.1007/s00432-021-03888-w. Epub 2022 Jan 20.


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.

Keywords: Carcinogenesis; Colorectal cancer; Epigenome; Genome; Hereditary; Pathway; Routes.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease*
  • Humans
  • Microsatellite Instability*


  • Biomarkers, Tumor