Frequent Activating Mutations of PIK3CA in Ovarian Clear Cell Carcinoma

被引：412

作者：

Kuo, Kuan-Ting ^{[1
,5
]}

Mao, Tsui-Lien ^{[5
]}

Jones, Sian ^{[3
]}

Veras, Emanuela ^{[1
]}

Ayhan, Ayse ^{[6
]}

Wang, Tian-Li ^{[2
]}

Glas, Ruth ^{[7
]}

Slamon, Dennis ^{[7
]}

Velculescu, Victor E. ^{[3
,4
]}

Kuman, Robert J. ^{[1
,2
]}

Shih, Ie-Ming ^{[1
,2
]}

机构：

[1] Johns Hopkins Med Inst, Kimmel Canc Ctr, Dept Pathol, Baltimore, MD 21205 USA

[2] Johns Hopkins Med Inst, Kimmel Canc Ctr, Dept Obstet Gynecol, Baltimore, MD 21205 USA

[3] Johns Hopkins Med Inst, Kimmel Canc Ctr, Ludwig Ctr, Baltimore, MD 21205 USA

[4] Johns Hopkins Med Inst, Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21205 USA

[5] Natl Taiwan Univ Hosp, Dept Pathol, Taipei 100, Taiwan

[6] Seirei Maikatahara Hosp, Dept Pathol, Hamamatsu, Shizuoka, Japan

[7] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2009年 / 174卷 / 05期

关键词：

PHOSPHATIDYLINOSITOL 3-KINASE/MAMMALIAN TARGET; DISTINCT-HISTOLOGIC-TYPE; PHOSPHOINOSITIDE; 3-KINASE; RAPAMYCIN INHIBITOR; POOR-PROGNOSIS; HUMAN CANCERS; P53; MUTATION; RESISTANCE; GENE; KRAS;

D O I：

10.2353/ajpath.2009.081000

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

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, PIK3C4, 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 fines. Sequence mutations of PIK3C4, TP53, KRAS, PTEN, CTNNB1, and BRAF occurred in 33%, 15%, 7%, 5%, 3%, and 1% of CCC cases, respectively. Sequence analysis of PIK3C4 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. (Am J Pathol 2009, 174:1597-1601; DOI. 10.2353/ajpath.2009.081000)

引用

页码：1597 / 1601

页数：5

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