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, lungand 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 AKT1E17K variant was mutually exclusive with respect to the PIK3CA E454K or H1047R alleles and was present only in ductal and lobular histotypes. Our results, showingthat 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 AKT1 E17K variant could be effective mainly in specific cancer types.

AKT1 (E17K) in human solid tumours

LAMBA, SIMONA ELENA;BARDELLI, Alberto
2008

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, lungand 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 AKT1E17K variant was mutually exclusive with respect to the PIK3CA E454K or H1047R alleles and was present only in ductal and lobular histotypes. Our results, showingthat 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 AKT1 E17K variant could be effective mainly in specific cancer types.
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http://www.nature.com/onc/journal/v27/n42/full/onc2008170a.html
AKT1; PIK3CA; mutation; cancer
Bleeker FE; Felicioni L; Buttitta F; Lamba S; Cardone L; Rodolfo M; Scarpa A; Leenstra S; Frattini M; Barbareschi M; Del Grammastro M; Sciarrotta MG; Zanon C; Marchetti A; Bardelli A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/44726
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