AKT1E17K in human solid tumours

F. E. Bleeker, L. Felicioni, F. Buttitta, S. Lamba, L. Cardone, M. Rodolfo, A. Scarpa, S. Leenstra, M. Frattini, M. Barbareschi, M. Del Grammastro, M. G. Sciarrotta, C. Zanon, A. Marchetti, A. Bardelli

Research output: Contribution to journalArticle

Abstract

The serine-threonine kinase AKT1 is a central player in the oncogenic pathway controlled by PI3K. Recently, a somatic mutation in AKT1 (E17K) has been detected in breast, colorectal, lung and ovarian cancers. The E17K change results in constitutive AKT1 activation and induces leukaemia in mice. We determined the occurrence of the E17K variant in a panel of 764 tumour samples. These included breast, lung, ovarian, colorectal and pancreatic carcinomas as well as melanomas and glioblastomas. Despite the fact that these tumours are known to bear alterations in genes involved in the PI3K signalling pathway, AKT1E17K was detected only in breast (16/273), colorectal (1/88) and lung (1/155) cancers. Within the neoplasms of breast origin, the AKT1 E17K variant was mutually exclusive with respect to the PIK3CA E454KorH1047R alleles and was present only in ductal and lobular histotypes. Our results, showing that AKT1 mutations seem to occur in a tissue-specific fashion have basic and clinical implications. First, the activity of mutated AKT1 in oncogenic PI3K signalling could be strictly dependent on the cell and tissue milieu. Second, therapeutic efforts aimed at selective targeting the AKT1E17K variant could be effective mainly in specific cancer types.

Original languageEnglish
Pages (from-to)5648-5650
Number of pages3
JournalOncogene
Volume27
Issue number42
DOIs
Publication statusPublished - Sep 18 2008

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Phosphatidylinositol 3-Kinases
Colorectal Neoplasms
Neoplasms
Breast
Breast Neoplasms
Lung
Mutation
Protein-Serine-Threonine Kinases
Glioblastoma
Ovarian Neoplasms
Melanoma
Lung Neoplasms
Leukemia
Alleles
Genes
Therapeutics

Keywords

  • AKT1
  • Cancer
  • Mutation
  • PIK3CA

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Bleeker, F. E., Felicioni, L., Buttitta, F., Lamba, S., Cardone, L., Rodolfo, M., ... Bardelli, A. (2008). AKT1E17K in human solid tumours. Oncogene, 27(42), 5648-5650. https://doi.org/10.1038/onc.2008.170

AKT1E17K in human solid tumours. / Bleeker, F. E.; Felicioni, L.; Buttitta, F.; Lamba, S.; Cardone, L.; Rodolfo, M.; Scarpa, A.; Leenstra, S.; Frattini, M.; Barbareschi, M.; Grammastro, M. Del; Sciarrotta, M. G.; Zanon, C.; Marchetti, A.; Bardelli, A.

In: Oncogene, Vol. 27, No. 42, 18.09.2008, p. 5648-5650.

Research output: Contribution to journalArticle

Bleeker, FE, Felicioni, L, Buttitta, F, Lamba, S, Cardone, L, Rodolfo, M, Scarpa, A, Leenstra, S, Frattini, M, Barbareschi, M, Grammastro, MD, Sciarrotta, MG, Zanon, C, Marchetti, A & Bardelli, A 2008, 'AKT1E17K in human solid tumours', Oncogene, vol. 27, no. 42, pp. 5648-5650. https://doi.org/10.1038/onc.2008.170
Bleeker FE, Felicioni L, Buttitta F, Lamba S, Cardone L, Rodolfo M et al. AKT1E17K in human solid tumours. Oncogene. 2008 Sep 18;27(42):5648-5650. https://doi.org/10.1038/onc.2008.170
Bleeker, F. E. ; Felicioni, L. ; Buttitta, F. ; Lamba, S. ; Cardone, L. ; Rodolfo, M. ; Scarpa, A. ; Leenstra, S. ; Frattini, M. ; Barbareschi, M. ; Grammastro, M. Del ; Sciarrotta, M. G. ; Zanon, C. ; Marchetti, A. ; Bardelli, A. / AKT1E17K in human solid tumours. In: Oncogene. 2008 ; Vol. 27, No. 42. pp. 5648-5650.
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