Syndromic Colon Cancer: Lynch Syndrome and Familial Adenomatous Polyposis
Section snippets
Mismatch Mutation Repair Gene Function
Six MMR genes have been identified (Box 2). The two major genes are MLH1 and MSH2. The four minor MMR genes are MSH6, MSH3, PMS2, and MLH3. Mutations in MLH3 and MSH3 are not believed to cause malignancy [3]. MMR genes work as dimers or in pairs: MLH1 can pair with PMS2 or MLH3, whereas MSH2 can pair with MSH3 or MSH6. A mutation in MSH3 can therefore be overcome as MSH2 pairs with MSH6, and MSH6 mutations can be overcome by MSH2 pairing with MSH3 [3]. Similarly, a mutation in PMS2 can be
Lynch Syndrome: Clinical Presentation and Diagnosis
Insofar as every patient who has colon cancer should undergo a detailed family history, the Amsterdam criteria, listed in Box 1, represents the starting point for evaluating the genetic basis of colon cancer. Genetic testing, however, reveals MMR gene mutations in only half of patients who meet the Amsterdam criteria [10]. Conversely, at least half of patients who have genetic mutations that define Lynch syndrome do not meet the Amsterdam criteria [11], [12], [13], [14]. The Amsterdam criteria
Classical Familial Adenomatous Polyposis
FAP is a dominantly inherited syndrome in which affected people develop hundreds, if not thousands, of colonic polyps that inevitably lead to colon cancer at a relatively young age. It is caused by mutations of the APC gene, a tumor-suppressor gene located on chromosome 5q21-q22 [101]. The APC gene normally blocks DNA transcription that would otherwise lead to uncontrolled cellular growth, helps control cell adhesion, and helps regulate migration of enterocytes [102]. APC gene mutation and
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