title: Mutations of the PIK3CA gene in hereditary colorectal cancers.
abstract: Somatic mutations of the PIK3CA gene have recently been detected in various human cancers, including sporadic colorectal cancer. However, mutations of the PIK3CA gene in hereditary colorectal cancers have not been clarified. To elucidate the mutation status in familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC), which are the most common hereditary colorectal cancers, we investigated PIK3CA mutations in 163 colorectal tumors, including adenomas, intramucosal carcinomas and invasive carcinomas. For comparison, we also analyzed mutations of the same gene in 160 sporadic colorectal tumors at various histopathological stages. Analysis at exons 1, 7, 9 and 20 of the PIK3CA gene revealed somatic mutations in 21% (8 of 39) of FAP invasive carcinomas, 21% (7 of 34) of HNPCC invasive carcinomas, 15% (8 of 52) of sporadic invasive carcinomas, and 14% (7 of 50) of sporadic colorectal metastases in the liver. Mutations in FAP and HNPCC carcinomas predominantly occurred in the kinase domain (exon 20), while the majority of mutations in sporadic cases occurred in the helical domain (exon 9). Adenomas and intramucosal carcinomas from all patients exhibited no mutations (0 of 148). Our data suggest that PIK3CA mutations contribute to the invasion step from intramucosal carcinoma to invasive carcinoma in colorectal carcinogenesis in FAP and HNPCC patients at a similar extent to that seen in sporadic patients.
authors.affiliation: Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. mmiyaki@opal.famille.ne.jp
authors.forename: Michiko
authors.initials: M
authors.lastname: Miyaki
authors.forename: Takeru
authors.initials: T
authors.lastname: Iijima
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Yamaguchi
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: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D058534:Class I Phosphatidylinositol 3-Kinases; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000473:pathology; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D009154:Mutation; D020125:Mutation, Missense; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human