AKT1 pleckstrin homology domain E17K activating mutation in endometrial carcinoma

Gynecol Oncol. 2010 Jan;116(1):88-91. doi: 10.1016/j.ygyno.2009.09.038. Epub 2009 Oct 22.


Objectives: The PI3K/AKT pathway is frequently activated in endometrial carcinoma (EC) mainly due to mutations in the PIK3CA and PTEN genes. These events are common and believed to be the key to endometrial carcinogenesis. Recently, a somatic activating mutation in the AKT1 gene (E17K) was identified in several cancer types. In this study we explored the frequency of this AKT1 mutation in endometrial carcinoma.

Methods: Tumor DNA, extracted from 73 EC was analyzed for AKT1 E17K mutation (G49A) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition, the tumors were screened for coexisting common mutations in PTEN, PIK3CA and KRAS.

Results: The AKT1 E17K mutation was detected in 4% of EC. One of the AKT1-mutated tumors showed coexisting PTEN loss-of-function mutation.

Conclusion: We identified the AKT1 E17K mutation in 4% of endometrial carcinomas. The presence of double AKT1/ PTEN mutants is in accord with the hypothesis that in EC more than one hit is required to completely activate the PI3K pathway. Furthermore, AKT1 mutations were limited to high grade, advanced stage tumors suggesting that this mutation confers a more aggressive tumor behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Proteins / genetics
  • DNA, Neoplasm / genetics
  • Endometrial Neoplasms / enzymology
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Mutation*
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphoproteins / genetics
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Blood Proteins
  • DNA, Neoplasm
  • Phosphoproteins
  • platelet protein P47
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human