title: Working through a diagnostic challenge: colonic polyposis, Amsterdam criteria, and a mismatch repair mutation.
abstract: The two most common causes of hereditary colorectal cancer are Lynch syndrome and familial adenomatous polyposis (FAP). The phenotype of Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is differentiated in part from FAP by the lack of profuse colonic polyposis. Here we describe a proband who presented with greater than 50 adenomatous colonic polyps prior to developing cancer of the colon and urinary bladder, and a family history that fulfills the Amsterdam criteria. Germline analyses of APC and MYH in the proband did not reveal any mutations. Comprehensive analysis of the mismatch repair genes associated with Lynch syndrome revealed a germline hMSH6 missense mutation 2314C>T (arg772trp) and normal sequencing for hMSH2 and hMLH1. We outline evidence supporting the pathogenicity of the identified hMSH6 mutation (arg772trp) and suggest possible etiologies for the unexplained colonic adenomatous polyposis.
authors.affiliation: Department of Clinical Cancer Genetics, City of Hope National Medical Center, Duarte, CA, USA, Kory.jasperson@hci.utah.edu
authors.forename: Kory W
authors.initials: KW
authors.lastname: Jasperson
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Blazer
authors.forename: Katrina
authors.initials: K
authors.lastname: Lowstuter
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weitzel
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics; D011125:Adenomatous Polyposis Coli / Q000150:complications* / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D001749:Urinary Bladder Neoplasms / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein