Lynch syndrome is an autosomal dominantly inherited cancer susceptibility syndrome, characterized by cancers of multiple anatomic sites, of which colorectal cancer (CRC) is the most common. Mismatch repair (MMR) genes, inclusive of MLH2, MLH1, PMS2, and MSH6, in their mutant form are causal for the cancer phenotype (See also DNA Damage Response Genes, Mismatch Repair in Genetic Instability). More recently, it has been found that deletions in the EPCAM gene can silence MSH2 (Ligtenberg et al. 2009; Lynch et al. 2011) (See also EpCAM). Lynch syndrome appears to show genotypic and phenotypic heterogeneity. MSH2 mutations may predispose to a greater frequency of extracolonic cancers, while mutations in MSH6may result in a predominance of gynecologic cancer, particularly endometrial carcinoma, so that CRC may not pose the primary basis for Lynch syndrome diagnosis. Lynch syndrome is the most commonly occurring CRC...
KeywordsFamilial Adenomatous Polyposis Lynch Syndrome MUTYH Mutation Lynch Syndrome Patient Lynch Syndrome Family
- Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2009) Recommendations from the EGAPP Working Group: genetic testing strategies in newly diagnosed individuals with colorectal cancer aimed at reducing morbidity and mortality from Lynch syndrome in relatives. Genet Med 11:35–41CrossRefGoogle Scholar
- Halvarsson B, Müller W, Planck M, Benoni AC, Mangell P, Ottosson J, Hallén M, Isinger A, Nilbert M (2007) Phenotypic heterogeneity in hereditary non-polyposis colorectal cancer: identical germline mutations associated with variable tumor morphology and immunohistochemical expression. J Clin Pathol 60:781–786PubMedCentralCrossRefPubMedGoogle Scholar
- Hegde M, Ferber M, Mao R, Samowitz W, Ganguly A, A Working Group of the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee (2014) ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis). Genet Med 16:101–115CrossRefPubMedGoogle Scholar
- Ligtenberg MJL, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TYH, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJB, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JHJM, Leung SY, Hoogerbrugge N (2009) Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1. Nat Genet 41:112–117CrossRefPubMedGoogle Scholar
- Lynch H, Riegert-Johnson D, Snyder C, Lynch J, Hagenkord J, Boland CR, Rhees J, Thibodeau S, Boardman L, Davies J, Kuiper RP, Hoogerbrugge N, Ligtenberg M (2011) Lynch syndrome associated extracolonic tumors are rare in two extended families with the same EPCAM deletion. Am J Gastroenterol 106:1829–1836PubMedCentralCrossRefPubMedGoogle Scholar
- Schmeler KM, Lynch HT, Chen L-M, Munsell MF, Soliman PT, Clark MB, Daniels MS, White KG, Boyd-Rogers SG, Conrad PG, Yang KY, Rubin MM, Sun CC, Slomovitz BM, Gershenson DM, Lu KH (2006) Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 354:261–269CrossRefPubMedGoogle Scholar