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Molecular Pathogenesis of Colorectal Cancer pp 1–24Cite as

The Genetics of Colorectal Cancer

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Abstract

Colorectal cancer (CRC) develops over a period of years through a defined progression from a single aberrant crypt to a benign adenoma and ultimately to an invasive malignancy. These phenotypic steps parallel a series of underlying changes at the DNA level. Many of the critical tumor suppressor loci have been identified through cytogenetic or genetic linkage studies of inherited disorders that predispose affected family members to the development of benign or malignant lesions in the colorectal epithelium. Inactivating mutations in the APC gene not only were first identified in the germline of individuals with familial adenomatous polyposis coli but also are present in most sporadic CRCs. Germline mutations in MSH2, MLH1, MSH6, or PMS2 predispose individuals with Lynch syndrome to CRCs with DNA mismatch repair defects; these genes can be mutated or silenced in sporadic CRCs as well. Other inherited mutations are responsible for benign colorectal lesions that rarely progress to malignancy, including those found in the SMAD4, BMPR1A, and PTEN genes. Sporadic changes in these genes are found in malignant rather than premalignant lesions, suggesting that these mutations promote rather than initiate tumorigenesis. Genetic analysis of CRCs will permit stratification for improved prognosis and treatment.

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  1. Department of Molecular Immunology, Virology & Medical Genetics, The Ohio State University College of Medicine, 460 West 12th Avenue, 986 Biomedical Research Tower, Columbus, OH, USA

    William Hankey & Joanna Groden

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  1. William Hankey
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  2. Joanna Groden
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Correspondence to Joanna Groden .

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  1. Molecular Pathology Unit, Harvard Medical School, Charlestown, Massachusetts, USA

    Kevin M. Haigis, Ph.D.

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Hankey, W., Groden, J. (2013). The Genetics of Colorectal Cancer. In: Haigis, Ph.D., K. (eds) Molecular Pathogenesis of Colorectal Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8412-7_1

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