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Genomic landscape of colorectal carcinogenesis

  • Review – Cancer Research
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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

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.

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Authors and Affiliations

  1. Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea

    Jin Cheon Kim

  2. Laboratory of Cancer Biology and Genetics, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea

    Jin Cheon Kim

  3. Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK

    Walter F. Bodmer

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Conception and design: JCK; manuscript writing: JCK and WFB; final approval of manuscript: JCK and WFB. Accountable for all aspects of the work: JCK and WFB.

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Correspondence to Jin Cheon Kim or Walter F. Bodmer.

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Kim, J.C., Bodmer, W.F. Genomic landscape of colorectal carcinogenesis. J Cancer Res Clin Oncol 148, 533–545 (2022). https://doi.org/10.1007/s00432-021-03888-w

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