Our findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users.
These findings did not provide evidence of a possible role of COMT Val<sup>158</sup>Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis.
To show the involvement of AKT1(E17K) directly in v-Abl-mediated tumorigenesis, we infected bone marrow cells from mice with bicistronic retroviruses encoding v-Abl and either wild-type or the mutant AKT1.
Overall, the evidence indicates that the molecular mechanism underlying E17Koncogenesis is a broadened target lipid selectivity that allows high-affinity binding to PI(4,5)P(2).
Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=-1.2, SE 0.4, p=0.003).
Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms.
Our findings provide strong support for the initial report that genetic variation at rs2494732 of AKT1 influences the risk of developing a psychotic disorder in cannabis users.
In a case-control study of 489 first-episode psychosis patients and 278 control subjects, we investigated the interaction between variation at the AKT1 rs2494732 single nucleotide polymorphism and cannabis use in increasing the risk of psychosis.
Follow-up analysis supported AKT1 rs2494732 × cannabis interaction in the case-only (β = 0.20; P = .007), case-sibling (interaction P = .040), and case-control (interaction P = .057) analyses, with individuals with C/C genotypes having an approximately 2-fold odds of being diagnosed with a psychotic disorder when having used cannabis.
Results In patients with AKT1 E17K-mutant tumors (n = 52) and a median of five lines of prior therapy, the median PFS was 5.5 months (95% CI, 2.9 to 6.9 months), 6.6 months (95% CI, 1.5 to 8.3 months), and 4.2 months (95% CI, 2.1 to 12.8 months) in patients with estrogen receptor-positive breast, gynecologic, and other solid tumors, respectively.
AKT1 E17K in Colorectal Carcinoma Is Associated with BRAF V600E but Not MSI-H Status: A Clinicopathologic Comparison to PIK3CA Helical and Kinase Domain Mutants.
Our data provide evidence that, although AKT1 mutations are apparently rare in lung cancer (1.9%), the oncogenic properties of E17K-AKT1 may contribute to the development of a fraction of lung carcinoma with squamous histotype (5.5%).
Both maintained T-cell responses in peripheral blood to oncogenic driver mutations - BRAF-N581I in the NSCLC and AKT1-E17K in the CRC - years after treatment initiation.
Here, we selectively disrupt the ability of rapidly proliferating cancer cells to spawn AKT1<sup>low</sup> daughter cells that are rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using β1-integrin activation and the AKT1-E17K-mutant oncoprotein as experimental tools <i>in vivo</i> Surprisingly, we find that selective depletion of AKT1<sup>low</sup> slow proliferators actually reduces the growth of a molecularly diverse panel of human cancer cell xenograft models without globally altering cell proliferation or survival <i>in vivo</i> Moreover, we find that unusual cancer patients with AKT1-E17K-mutant solid tumors also fail to produce AKT1<sup>low</sup> quiescent cancer cells and that this correlates with significantly prolonged survival after adjuvant treatment compared with other patients.
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.