title: AKT1(E17K) in human solid tumours.
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, AKT1(E17K) 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(E454K or H1047R) 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 AKT1(E17K) variant could be effective mainly in specific cancer types.
authors.affiliation: Laboratory of Molecular Genetics, The Oncogenomics Center, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy.
authors.forename: F E
authors.initials: FE
authors.lastname: Bleeker
authors.forename: L
authors.initials: L
authors.lastname: Felicioni
authors.forename: F
authors.initials: F
authors.lastname: Buttitta
authors.forename: S
authors.initials: S
authors.lastname: Lamba
authors.forename: L
authors.initials: L
authors.lastname: Cardone
authors.forename: M
authors.initials: M
authors.lastname: Rodolfo
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
authors.forename: S
authors.initials: S
authors.lastname: Leenstra
authors.forename: M
authors.initials: M
authors.lastname: Frattini
authors.forename: M
authors.initials: M
authors.lastname: Barbareschi
authors.forename: M Del
authors.initials: MD
authors.lastname: Grammastro
authors.forename: M G
authors.initials: MG
authors.lastname: Sciarrotta
authors.forename: C
authors.initials: C
authors.lastname: Zanon
authors.forename: A
authors.initials: A
authors.lastname: Marchetti
authors.forename: A
authors.initials: A
authors.lastname: Bardelli
mesh_terms: D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D009928:Organ Specificity; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt