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

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