https://scholars.lib.ntu.edu.tw/handle/123456789/473646
標題: | Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma | 作者: | KUAN-TING KUO TSUI-LIEN MAO Jones S. Veras E. Ayhan A. Wang T.-L. Glas R. Slamon D. Velculescu V.E. Kuman R.J. Shih I.-M. |
公開日期: | 2009 | 出版社: | American Society for Investigative Pathology Inc. | 卷: | 174 | 期: | 5 | 起(迄)頁: | 1597-1601 | 來源出版物: | American Journal of Pathology | 摘要: | Ovarian clear cell carcinoma (CCC) is one of the most malignant types of ovarian carcinomas, particularly at advanced stages. Unlike the more common type of ovarian cancer, high-grade serous carcinoma, ovarian CCC is often resistant to platinum-based chemotherapy, and therefore an effective treatment for this tumor type at advanced stages is urgently needed. In this study, we analyzed 97 ovarian CCCs for sequence mutations in KRAS, BRAF, PIK3CA, TP53, PTEN, and CTNNB1 as these mutations frequently occur in other major types of ovarian carcinomas. The samples included 18 CCCs for which affinity-purified tumor cells from fresh specimens were available, 69 microdissected tumors from paraffin tissues, and 10 tumor cell lines. Sequence mutations of PIK3CA, TP53, KRAS, PTEN, CTNNB1, and BRAF occurred in 33%, 15%, 7%, 5%, 3%, and 1% of CCC cases, respectively. Sequence analysis of PIK3CA in 28 affinity-purified CCCs and CCC cell lines showed a mutation frequency of 46%. Samples with PIK3CA mutations showed intense phosphorylated AKT immunoreactivity. These findings demonstrate that ovarian CCCs have a high frequency of activating PIK3CA mutations. We therefore suggest that the use of PIK3CA-targeting drugs may offer a more effective therapeutic approach compared with current chemotherapeutic agents for patients with advanced-stage and recurrent CCC. Copyright ? American Society for Investigative Pathology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-65649128979&doi=10.2353%2fajpath.2009.081000&partnerID=40&md5=5fff8bead3caa350de4c2c05875c89ec https://scholars.lib.ntu.edu.tw/handle/123456789/473646 |
ISSN: | 0002-9440 | DOI: | 10.2353/ajpath.2009.081000 | SDG/關鍵字: | B Raf kinase; catenin; K ras protein; paraffin; phosphatidylinositol 3 kinase; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein p53; messenger RNA; phosphatidylinositol 3 kinase; PIK3CA protein, human; tumor marker; advanced cancer; article; clear cell carcinoma; gene mutation; gene sequence; human; human tissue; immunoreactivity; major clinical study; ovary carcinoma; priority journal; recurrent cancer; sequence analysis; adenocarcinoma; colloid carcinoma; comparative study; cystadenocarcinoma; endometrioid carcinoma; enzyme immunoassay; female; genetics; metabolism; mutation; ovary tumor; pathology; phosphorylation; prognosis; reverse transcription polymerase chain reaction; single nucleotide polymorphism; 1-Phosphatidylinositol 3-Kinase; Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Female; Humans; Immunoenzyme Techniques; Mutation; Ovarian Neoplasms; Phosphorylation; Polymorphism, Single Nucleotide; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Markers, Biological |
顯示於: | 病理學科所 |
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