title: Identification and characterization of a novel germline p53 mutation in a patient with glioblastoma and colon cancer.
abstract: Germline mutations in the p53 tumor suppressor gene have been identified in patients with Li-Fraumeni syndrome (LFS) and patients with Li-Fraumeni-like syndrome (LFL). However, to date, germline p53 mutations in patients not fulfilling the criteria of LFS or LFL have been reported only very rarely. In our study, a novel germline c.584T>C (p.Ile195Thr) mutation of the p53 gene was found in a 21-year-old male with a glioblastoma and colon cancer. He had no family history of cancer within second-degree relatives, and loss of the wild-type p53 allele and overexpression of p53 protein were observed in both tumors. Functional analyses revealed transactivation and growth suppressive function activities of the Thr195-type p53 to be impaired. These results suggest germline p53 mutations to possibly be responsible for a subset of young adult patient with multiple malignant tumors, even those not meeting the clinical criteria for LFS or LFL.
authors.affiliation: First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kurachi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tsuneyoshi
authors.forename: Naoki
authors.initials: N
authors.lastname: Yokota
authors.forename: Masato
authors.initials: M
authors.lastname: Maekawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000328:Adult; D003110:Colonic Neoplasms / Q000235:genetics*; D003114:Colony-Forming Units Assay; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D008156:Luciferases / Q000378:metabolism; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases