|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
To enable prospective screening for the low prevalence AKT1 E17K mutation, we have developed and validated a competitive allele-specific TaqMan® PCR (castPCR™) assay for mutation detection in formalin-fixed paraffin-embedded (FFPE) tumor tissue.
|
28472036 |
2017 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Although AKT1-mutant tumor specimens were often found to harbor concurrent alterations in other driver genes, a subset of specimens harboring AKT1 (E17K) as the only known driver alteration was also identified.
|
27515171 |
2016 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Compound 21a also served as a potent inhibitor of the AKT1-E17K mutant protein and inhibited tumor growth in a human xenograft mouse model of endometrial adenocarcinoma.
|
27305487 |
2016 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The results showed that activating mutations in either PIK3CA or AKT1 were identified in 20 tumors (67%); 19 tumors had PIK3CA mutations (63%; 13 in exon 20 and 6 in exon 9), and 1 had an AKT1 E17K mutation (3%).
|
27184479 |
2016 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The data show that tumors with AKT1(E17K) mutations are rational therapeutic targets for AKT inhibitors, although combinations with other targeted agents may be required where activating oncogenic mutations of other proteins are present in the same tumor.
|
26351323 |
2015 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The AKT1 (E17K) mutation in the tumor was not detectable in all investigated specimens.
|
26077595 |
2015 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here we report that in immortalized human bronchial epithelial cells (BEAS-2B cells) mutant AKT1-E17K promotes anchorage-dependent and -independent proliferation, increases the ability to migrate, invade as well as to survive and duplicate in stressful conditions, leading to the emergency of cells endowed with the capability to form aggressive tumours at high efficiency.
|
26053093 |
2015 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Knockin of the AKT1 E17K hotspot mutation on this PIK3CA wild-type background restored pathway signaling, proliferation, and tumor growth in vivo.
|
23888070 |
2013 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The AKT1 (E17K) mutation has been reported in some tumour types (breast, colorectal, ovarian and lung cancers), and it is of interest which tumour types other than those possess the E17K mutation.
|
19491896 |
2009 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
Recently, a somatic mutation in the AKT1 gene (E17K) was identified in a small proportion of human tumors.
|
19420344 |
2009 |
|
rs121434592
|
|
Neoplasms
|
|
0.100 |
GeneticVariation
|
BEFREE |
The activity of the endogenous kinase carrying the E17K mutation immunoprecipitated by tumour tissue was significantly higher compared with the wild-type kinase immunoprecipitated by the adjacent normal tissue as determined both by in vitro kinase assay using a consensus peptide as substrate and by in vivo analysis of the phosphorylation status of AKT1 itself (pT308, pS473) or of known downstream substrates such as GSK3 (pS9/S22) and p27 (T198).
|
18256540 |
2008 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
The results obtained in this study suggest that Akti-1/2 might be a better inhibitor for the treatment of BC caused by the E17K mutation in AKT1.
|
31698236 |
2019 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
AKT1 mutations (E17K) have been found in 1.4-8% of breast cancer patients.
|
29086897 |
2018 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
The data suggest that AKT1 (E17K) is the most likely disease driver in certain breast cancer patients.
|
27515171 |
2016 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
Analysis of TCGA breast cancer data revealed that the mRNA expression, total protein levels, and phosphorylation of various RTKs are decreased in human tumors harboring AKT1(E17K).
|
27004402 |
2016 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
Both AKT inhibitors caused highly significant growth inhibition of breast cancer explant models with AKT1(E17K) mutation.
|
26351323 |
2015 |
|
rs121434592
|
|
Breast Carcinoma
|
|
0.060 |
GeneticVariation
|
BEFREE |
AKT1 E17K is a bona fide oncogene in a human luminal breast cancer context.
|
23888070 |
2013 |
|
rs121434592
|
|
Malignant Neoplasms
|
|
0.050 |
GeneticVariation
|
BEFREE |
Conclusion This study provides the first clinical data that AKT1 E17K is a therapeutic target in human cancer.
|
28489509 |
2017 |
|
rs121434592
|
|
Malignant Neoplasms
|
|
0.050 |
GeneticVariation
|
BEFREE |
Recently, the E17K mutation in the AKT1 has been associated with multiple human malignancies and leukemia in mice.
|
20440266 |
2010 |
|
rs121434592
|
|
leukemia
|
|
0.050 |
GeneticVariation
|
BEFREE |
Recently, the E17K mutation in the AKT1 has been associated with multiple human malignancies and leukemia in mice.
|
20440266 |
2010 |
|
rs121434592
|
|
Malignant Neoplasms
|
|
0.050 |
GeneticVariation
|
BEFREE |
Recently, a somatic activating mutation in the AKT1 gene (E17K) was identified in several cancer types.
|
19853286 |
2010 |
|
rs121434592
|
|
leukemia
|
|
0.050 |
GeneticVariation
|
BEFREE |
The E17K change results in constitutive AKT1 activation, induces leukaemia in mice, and accordingly, may be therapeutically exploited to target the PI3K pathway.
|
19461960 |
2009 |
|
rs121434592
|
|
Malignant Neoplasms
|
|
0.050 |
GeneticVariation
|
BEFREE |
Overall, we detected the four AKT1 E17K</span> mutations in the breast cancers (4/93; 4.3%), but none in other cancers.
|
18392055 |
2008 |
|
rs121434592
|
|
leukemia
|
|
0.050 |
GeneticVariation
|
BEFREE |
The transforming mutation E17K/AKT1 is not a major event in B-cell-derived lymphoid leukaemias.
|
18665177 |
2008 |
|
rs121434592
|
|
Malignant Neoplasms
|
|
0.050 |
GeneticVariation
|
BEFREE |
Despite the major role of the AKT/PKB family of proteins in the regulation of many growth and survival mechanisms in the cell, and the increasing evidence suggesting that AKT disruption could play a key role in many human malignancies, no major mutations of AKT genes had been reported, until very recently when Carpten et al reported a novel transforming mutation (E17K) in the pleckstrin homology domain of the AKT1 gene in solid tumours.
|
18665177 |
2008 |