Cancer, growth and neurological disorders

Proteus Syndrome; Schizophrenia; Leopard Syndrome

Breast; Thymoma; Colorectal; Ovarian; Ovarian Serous Cystadenocarcinoma; Cystadenocarcinoma; Anal Squamous Cell Carcinoma; Cowden Syndrome 6; Cowden Syndrome 1; Melanoma; Leukemia

AKT1 is a known oncoprotein (OP). Cancer-related mutations in human tumours point to a gain of function of the protein kinase. The active form of the protein kinase normally acts to promote tumour cell proliferation. AKT1 is among the earliest recognized oncoproteins, with a homologue encoded by the v-Akt murine thymoma viral oncogene in the AKT8 retrovirus. up-regulation of PI3K/AKT pathways has been implicated in a variety of cancers. It is primarily mutated in human cancers at the E17, which is located within its PH domain. The E17K mutation is observed in breast cancer, colorectal and ovarian cancer. This somatic mutation results in increased phosphorylation at T308, higher phosphotransferase activity and higher basal ubiquitination. Loss of membrane localization of Akt1 is associated with Q20 mutation. Amplification of AKT1 has been described in human gastric adenocarcinoma, in lung and other cancers.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= +69, p<0.001); Brain oligodendrogliomas (%CFC= -51, p<0.012); Breast epithelial cell carcinomas (%CFC= +49, p<0.024); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +458, p<0.0001); Skin fibrosarcomas (%CFC= +105); and Skin melanomas - malignant (%CFC= +954, p<0.0001). The COSMIC website notes an up-regulated expression score for AKT1 in diverse human cancers of 544, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 247 for this protein kinase in human cancers was 4.1-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Percent mutation rates per 100 amino acids length in human cancers: 0.24 % in 46465 diverse cancer specimens. This rate is 3.2-fold higher than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 1.62 % in 1428 Meninges cancers tested; 0.81 % in 1945 skin cancers tested; 0.71 % in 353 bone cancers tested; 0.64 % in 4953 breast cancers tested; 0.51 % in 1030 urinary tract cancers tested; 0.46 % in 991 endometrium cancers tested; 0.25 % in 3006 large intestine cancers tested; 0.23 % in 1249 thyroid cancers tested; 0.08 % in 6100 lung cancers tested.

Most frequent mutations with the number of reports indicated in brackets: E17K (449).

No deletions, insertions or complex mutations are noted on the COSMIC website.