Hayano Takahide, Yokota Yuki, Hosomichi Kazuyoshi, Nakaoka Hirofumi, Yoshihara Kosuke, Adachi Sosuke, Kashima Katsunori, Tsuda Hitoshi, Moriya Takuya, Tanaka Kenichi, Enomoto Takayuki, Inoue Ituro
Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
PLoS One. 2014 Dec 2;9(12):e114491. doi: 10.1371/journal.pone.0114491. eCollection 2014.
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.
高级别浆液性卵巢癌（HGSOC）是上皮性卵巢癌中侵袭性最强的组织学类型，其特征是体细胞TP53突变频率很高。我们对34例日本HGSOC患者的肿瘤组织及配对的正常组织进行了外显子组分析，发现相当一部分患者没有TP53突变（24%，8/34）。结合拷贝数变异分析结果，我们将34例HGSOC患者细分为ST1和ST2亚型。ST1显示p53通路完整，其特征是体细胞突变和拷贝数改变较少。相比之下，ST2中的p53通路受损，其特征是体细胞突变和拷贝数改变丰富。基因表达谱结合使用基因本体资源的分析表明，特定的生物学过程（有丝分裂和DNA解旋酶）与基因组稳定性和癌症病因相关。特别是，我们证明了存在一种新型的HGSOC患者亚型，其特征是p53通路完整，基因组改变有限且具有特定的基因表达谱。
