title: ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).
abstract: Lynch syndrome, familial adenomatous polyposis, and Mut Y homolog (MYH)-associated polyposis are three major known types of inherited colorectal cancer, which accounts for up to 5% of all colon cancer cases. Lynch syndrome is most frequently caused by mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 and is inherited in an autosomal dominant manner. Familial adenomatous polyposis is manifested as colonic polyposis caused by mutations in the APC gene and is also inherited in an autosomal dominant manner. Finally, MYH-associated polyposis is caused by mutations in the MUTYH gene and is inherited in an autosomal recessive manner but may or may not be associated with polyps. There are variants of both familial adenomatous polyposis (Gardner syndrome--with extracolonic features--and Turcot syndrome, which features medulloblastoma) and Lynch syndrome (Muir-Torre syndrome features sebaceous skin carcinomas, and Turcot syndrome features glioblastomas). Although a clinical diagnosis of familial adenomatous polyposis can be made using colonoscopy, genetic testing is needed to inform at-risk relatives. Because of the overlapping phenotypes between attenuated familial adenomatous polyposis, MYH-associated polyposis, and Lynch syndrome, genetic testing is needed to distinguish among these conditions. This distinction is important, especially for women with Lynch syndrome, who are at increased risk for gynecological cancers. Clinical testing for these genes has progressed rapidly in the past few years with advances in technologies and the lower cost of reagents, especially for sequencing. To assist clinical laboratories in developing and validating testing for this group of inherited colorectal cancers, the American College of Medical Genetics and Genomics has developed the following technical standards and guidelines. An algorithm for testing is also proposed.
authors: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
authors: Madhuri
authors: M
authors: Hegde
authors: Mayo Clinic, Rochester, Minnesota, USA.
authors: Mathew
authors: M
authors: Ferber
authors: Mayo Clinic, Salt Lake City, Utah, USA.
authors: Rong
authors: R
authors: Mao
authors: Mayo Clinic, Salt Lake City, Utah, USA.
authors: Wade
authors: W
authors: Samowitz
authors: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors: Arupa
authors: A
authors: Ganguly
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000235:genetics; D000465:Algorithms; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000592:standards*; D019983:Guideline Adherence; D006801:Humans; D017410:Practice Guidelines as Topic; D014481:United States