The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas

被引:112
作者
Shoji, K. [1 ]
Oda, K. [1 ]
Nakagawa, S. [1 ]
Hosokawa, S. [1 ]
Nagae, G. [2 ]
Uehara, Y. [1 ]
Sone, K. [1 ]
Miyamoto, Y. [1 ]
Hiraike, H. [1 ]
Hiraike-Wada, O. [1 ]
Nei, T. [1 ]
Kawana, K. [1 ]
Kuramoto, H. [3 ]
Aburatani, H. [2 ]
Yano, T. [1 ]
Taketani, Y. [1 ]
机构
[1] Univ Tokyo, Dept Obstet & Gynecol, Bunkyo Ku, Tokyo 1138655, Japan
[2] Univ Tokyo, Adv Sci & Technol Res Ctr, Genome Sci Div, Meguro Ku, Tokyo 1538904, Japan
[3] Kitasato Univ, Grad Sch Med Sci, Dept Clin Cytol, Kanagawa 2288555, Japan
关键词
AKT1; mutation; PI3-kinase; endometrial carcinoma; CELL LUNG-CANCER; E17K MUTATION; MICROSATELLITE INSTABILITY; PIK3CA GENE; TRANSFORMING MUTATION; HIGH-FREQUENCY; PTEN; PATHWAY; METHYLATION; ADENOCARCINOMA;
D O I
10.1038/sj.bjc.6605109
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: The phosphatidylinositol 3'-kinase (PI3K)-AKT pathway is activated in many human cancers and plays a key role in cell proliferation and survival. A mutation (E17K) in the pleckstrin homology domain of the AKT1 results in constitutive AKT1 activation by means of localisation to the plasma membrane. The AKT1 ( E17K) mutation has been reported in some tumour types ( breast, colorectal, ovarian and lung cancers), and it is of interest which tumour types other than those possess the E17K mutation. METHODS: We analysed the presence of the AKT1 ( E17K) mutation in 89 endometrial cancer tissue specimens and in 12 endometrial cancer cell lines by PCR and direct sequencing. RESULTS: We detected two AKT1 ( E17K) mutations in the tissue samples ( 2 out of 89) and no mutations in the cell lines. These two AKT1 mutant tumours do not possess any mutations in PIK3CA, PTEN and K-Ras. INTERPRETATION: Our results and earlier reports suggest that AKT1 mutations might be mutually exclusive with other PI3K-AKT-activating alterations, although PIK3CA mutations frequently coexist with other alterations ( such as HER2, K-Ras and PTEN) in several types of tumours. British Journal of Cancer ( 2009) 101, 145-148. doi: 10.1038/sj.bjc.6605109 www.bjcancer.com Published online 2 June 2009 (C) 2009 Cancer Research UK
引用
收藏
页码:145 / 148
页数:4
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