The Oncogenic Mutation in the Pleckstrin Homology Domain of AKT1 in Endometrial Carcinomas

Br J Cancer. 2009 Jul 7;101(1):145-8. doi: 10.1038/sj.bjc.6605109. Epub 2009 Jun 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Proteins / genetics*
  • Cell Line, Tumor
  • DNA Methylation
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics*
  • Female
  • Humans
  • Mutation, Missense*
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / genetics*
  • Polymorphism, Single Nucleotide
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Blood Proteins
  • Phosphoproteins
  • platelet protein P47
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human