title: Contribution of bi-allelic germline MUTYH mutations to early-onset and familial colorectal cancer and to low number of adenomatous polyps: case-series and literature review.
abstract: In the absence of a polyposis phenotype, colorectal cancer (CRC) patients referred for genetic testing because of early-onset disease and/or a positive family history, typically undergo testing for molecular signs of Lynch syndrome in their tumors. In the absence of these signs, DNA testing for germline mutations associated with other known tumor syndromes is usually not performed. However, a few studies in large series of CRC patients suggest that in a small percentage of CRC cases, bi-allelic MUTYH germline mutations can be found in the absence of the MUTYH-associated polyposis phenotype. This has not been studied in the Dutch population. Therefore, we analyzed the MUTYH gene for mutations in 89 patients with microsatellite-low or stable CRC cancer diagnosed before the age of 40 years or otherwise meeting the Bethesda criteria, all of them without a polyposis phenotype. In addition, we studied a series of 693 non-CRC patients with 1-13 adenomatous colorectal polyps for the MUTYH hotspot mutations Y179C, G396D and P405L. No bi-allelic MUTYH mutations were observed. Our data suggest that the contribution of bi-allelic MUTYH mutations to the development of CRC in Dutch non-polyposis patients that meet clinical genetic referral criteria, and to the development of low number of colorectal adenomas in non-CRC patients, is likely to be low.
authors.affiliation: Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700RB, Groningen, The Netherlands.
authors.forename: A P
authors.initials: AP
authors.lastname: Knopperts
authors.forename: M
authors.initials: M
authors.lastname: Nielsen
authors.forename: R C
authors.initials: RC
authors.lastname: Niessen
authors.forename: C M J
authors.initials: CM
authors.lastname: Tops
authors.forename: B
authors.initials: B
authors.lastname: Jorritsma
authors.forename: J
authors.initials: J
authors.lastname: Varkevisser
authors.forename: J
authors.initials: J
authors.lastname: Wijnen
authors.forename: C L E
authors.initials: CL
authors.lastname: Siezen
authors.forename: R C
authors.initials: RC
authors.lastname: Heine-Bröring
authors.forename: H J
authors.initials: HJ
authors.lastname: van Kranen
authors.forename: Y J
authors.initials: YJ
authors.lastname: Vos
authors.forename: H
authors.initials: H
authors.lastname: Westers
authors.forename: E
authors.initials: E
authors.lastname: Kampman
authors.forename: R H
authors.initials: RH
authors.lastname: Sijmons
authors.forename: F J
authors.initials: FJ
authors.lastname: Hes
mesh_terms: D018256:Adenomatous Polyps / Q000235:genetics*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D055815:Young Adult
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase