A novel AKT3 mutation in melanoma tumours and cell lines

M. A. Davies, K. Stemke-Hale, C. Tellez, T. L. Calderone, W. Deng, V. G. Prieto, A. J.F. Lazar, J. E. Gershenwald, G. B. Mills

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

Abstract

Recently, a rare activating mutation of AKT1 (E17K) has been reported in breast, ovarian, and colorectal cancers. However, analogous activating mutations in AKT2 or AKT3 have not been identified in any cancer lineage. To determine the prevalence of AKT E17K mutations in melanoma, the most aggressive form of skin cancer, we analysed 137 human melanoma specimens and 65 human melanoma cell lines for the previously described activating mutation of AKT1, and for analogous mutations in AKT2 and AKT3. We identified a single AKT1 E17K mutation. Remarkably, a previously unidentified AKT3 E17K mutation was detected in two melanomas (from one patient) as well as two cell lines. The AKT3 E17K mutation results in activation of AKT when expressed in human melanoma cells. This represents the first report of AKT mutations in melanoma, and the initial identification of an AKT3 mutation in any human cancer lineage. We have also identified the first known human cell lines with naturally occurring AKT E17K mutations.

Original languageEnglish (US)
Pages (from-to)1265-1268
Number of pages4
JournalBritish Journal of Cancer
Volume99
Issue number8
DOIs
StatePublished - Oct 21 2008
Externally publishedYes

Keywords

  • AKT
  • Melanoma
  • Mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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