title: Difference in characteristics of APC mutations between colonic and extracolonic tumors of FAP patients: variations with phenotype.
abstract: To clarify the differences in characteristics of adenomatous polyposis coli (APC) mutations between colorectal tumors from various phenotypes of familial adenomatous polyposis (FAP) and between colorectal and extracolonic tumors, we analyzed APC mutations in 86 colorectal tumors from FAP patients including profuse, sparse and attenuated types, 23 sporadic colorectal tumors and 40 FAP extracolonic tumors including duodenal, gastric and desmoid tumors. In all tumors, 1 allele of the truncated APC gene retained armadillo repeats, 15-amino-acid (aa) repeats and various numbers of 20-aa repeats, but lacked SAMP repeats, as a result of germline and somatic mutations. Regarding 20-aa repeats, the truncated APC gene retained 1 repeat due to allele loss in 96% (27/28) of colorectal tumors from profuse-type FAP, 69% (36/52) of sparse-type retained 2 repeats due to somatic mutation, and 100% (6/6) of attenuated-type retained 2 or 3 repeats due to the third or second hit. In sporadic colorectal tumors 74% (17/23) retained 1 or 2 repeats. The truncated APC gene retained 3 repeats in 88% (7/8) of FAP duodenal tumors, 100% (26/26) of gastric tumors retained 2 or 3 repeats and 83% (5/6) of desmoid tumors retained 2 repeats. These data suggest that the number of beta-catenin downregulating 20-aa repeats in truncated APC gene associated with colorectal tumorigenesis is different in profuse, sparse and attenuated types of FAP, and that the association with tumorigenesis is also different between colorectal and extracolonic tumors.
authors.affiliation: Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo, Japan. mmiyaki@opal.famille.ne.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Miyaki
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Takeru
authors.initials: T
authors.lastname: Iijima
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Yasutome
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funata
authors.forename: Takeo
authors.initials: T
authors.lastname: Mori
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics; D015536:Down-Regulation; D018222:Desmoid Tumors / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin