title: Molecular characterization of an intact p53 pathway subtype in high-grade serous ovarian cancer.
abstract: High-grade serous ovarian cancer (HGSOC) is the most aggressive histological type of epithelial ovarian cancer, which is characterized by a high frequency of somatic TP53 mutations. We performed exome analyses of tumors and matched normal tissues of 34 Japanese patients with HGSOC and observed a substantial number of patients without TP53 mutation (24%, 8/34). Combined with the results of copy number variation analyses, we subdivided the 34 patients with HGSOC into subtypes designated ST1 and ST2. ST1 showed intact p53 pathway and was characterized by fewer somatic mutations and copy number alterations. In contrast, the p53 pathway was impaired in ST2, which is characterized by abundant somatic mutations and copy number alterations. Gene expression profiles combined with analyses using the Gene Ontology resource indicate the involvement of specific biological processes (mitosis and DNA helicase) that are relevant to genomic stability and cancer etiology. In particular we demonstrate the presence of a novel subtype of patients with HGSOC that is characterized by an intact p53 pathway, with limited genomic alterations and specific gene expression profiles.
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Hayano
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yokota
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yoshihara
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Kashima
authors.affiliation: Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Moriya
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Niigata Medical Center Hospital, Niigata, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53