AKT1E17K in human solid tumours

Bleeker, Fe; Felicioni, L; Buttitta, Fiamma; Lamba, Simona; Cardone, Luca; Rodolfo, Monica; Scarpa, Aldo; Leenstra, Sieger; Frattini, Milo; Barbareschi, Mattia; Grammastro, Maela Del; Sciarrotta, Mg; Zanon, Carlo; Marchetti, Antonio; Bardelli, Alberto

doi:10.1038/onc.2008.170

Cited by 189 publications

(139 citation statements)

References 13 publications

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“…Fifty to seventy percent of all Peutz-Jeghers syndrome 8 (PJS) cases are caused by germline mutations in the tumor suppressor gene STK11, also known as LKB1 [49][50][51]. STK11 is a serine/threonine kinase that via phosphorylation of AMPK activates TSC2, resulting in negative regulation of mTOR signaling.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Portrait of the PI3K/AKT pathway in colorectal cancer

Danielsen¹,

Eide²,

Nesbakken³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

233

200

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Section: Accepted Manuscriptmentioning

confidence: 99%

Portrait of the PI3K/AKT pathway in colorectal cancer

Danielsen¹,

Eide²,

Nesbakken³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

233

200

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“…Interestingly, AKT1 mutations recently identified in breast, ovarian and colorectal carcinoma are situated in the plekstrin homology domain (E17K), rather than in a kinase domain [17,[31][32][33]. Nevertheless, these AKT1 mutations are activating; they transform cells and induce leukemia in nude mice [17].…”

Section: Introductionmentioning

confidence: 98%

Phosphatidylinositol-3-kinase and AKT1 mutations occur early in breast carcinoma

Dunlap

Le²,

Shukla³

et al. 2009

Breast Cancer Res Treat

110

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Mutationally activated protein kinases are appealing therapeutic targets in breast carcinoma. Mutations in phosphatidylinositol-3-kinase (PI3KCA) have been described in 8-40% of invasive breast carcinomas, and AKT1 mutations have been characterized in 1-8% of breast carcinomas. However, there is little data on these mutations in breast precursor lesions. To further delineate the molecular evolution of breast tumorigenesis, samples of invasive breast carcinoma with an accompanying in situ component were macro dissected from formalin-fixed paraffin embedded tissue and screened for mutations in PIK3CA exons 7, 9, 20, and AKT1 exon 2. Laser capture micro dissection (LCM) was performed on mutation-positive carcinomas to directly compare the genotypes of separated invasive and in situ tumor cells. Among 81 cases of invasive carcinoma, there were eight mutations in PIK3CA exon 20 (7 H1047R, 1 H1047L) and four mutations in exon 9 (2 E545K, 1 E542K, 1 E545G), totaling 12/81 (14.8%). In 11 cases examined, paired LCM in situ tumor showed the identical PIK3CA mutation in invasive and in situ carcinoma. Likewise, 3 of 78 (3.8%) invasive carcinomas showed an AKT1 E17K mutation, and this mutation was identified in matching in situ carcinoma in both informative cases. Mutational status did not correlate with clinical parameters including hormone receptor status, grade, and lymph node status. The complete concordance of PIK3CA and AKT1 mutations in matched samples of invasive and in situ tumor indicates that these mutations occur early in breast cancer development and has implications with regard to therapeutics targeted to the PI3 kinase pathway.

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“…[5][6][7][8] As all of the four reported NSCLC tumors harboring the AKT1 E17K mutation had squamous cell carcinoma (SCC) histology, it was proposed that the AKT1 mutation may contribute to the development of SCC of the lung. 5,6 However, the total number of SCC cases investigated to date is insufficient to accurately estimate the frequency of the AKT1 E17K mutation.…”

mentioning

confidence: 99%