title: PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma.
abstract: Clear cell adenocarcinoma (CCA), a highly lethal histological subtype of ovarian carcinoma, is a type of human cancer with a high frequency of activating mutations in the PIK3CA gene. In this study, we aimed to determine how these mutations contribute to tumour development of CCAs. Exons 9 and 20 of the PIK3CA gene were analysed by direct genomic DNA sequencing of 23 CCAs with synchronous putative precursor lesions (ie endometriosis adjacent to carcinoma, with or without cytological atypia) and their mutational statuses were compared. Somatic mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all cases the type of mutation was H1047R in the kinase domain. The identical H1047R mutation was also detected in the coexisting endometriotic epithelium, adjacent to the CCAs, in nine of ten (90%) cases. Moreover, in six of the nine lesions, the H1047R mutation was identified even in the endometrioses lacking cytological atypia. These findings provide evidence that mutations of the PIK3CA gene occur in the putative precursor lesions of CCA, strongly suggesting that they are very early events in tumourigenesis, probably initiating the malignant transformation of endometriosis. A specific kinase inhibitor to mutated PIK3CA may potentially be an effective therapeutic reagent against these carcinomas.
authors: Department of Basic Pathology, National Defence Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan. dr21001@ndmc.ac.jp
authors: Sohei
authors: S
authors: Yamamoto
authors: Hitoshi
authors: H
authors: Tsuda
authors: Masashi
authors: M
authors: Takano
authors: Keichi
authors: K
authors: Iwaya
authors: Seiichi
authors: S
authors: Tamai
authors: Osamu
authors: O
authors: Matsubara
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000209:etiology / Q000235:genetics*; D000328:Adult; D058534:Class I Phosphatidylinositol 3-Kinases; D004715:Endometriosis / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human