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Integrated Genomic Analyses of Ovarian Carcinoma
It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Perturbations of the AKT signaling pathway in human cancer
Various pathogenic mechanisms contributing to activation of the AKT pathway in human malignancy as well as current pharmacologic strategies to target therapeutically components of this pathway are reviewed.
A retroviral oncogene, akt, encoding a serine-threonine kinase containing an SH2-like region.
Sequence analysis of v-akt and biochemical characterization of its product revealed that it codes for a protein kinase C-related serine-threonine kinase whose cellular homolog is expressed in most tissues, with the highest amount found in thymus, suggesting that Akt may form a functional link between tyrosine and serinesine phosphorylation pathways.
AKT plays a central role in tumorigenesis
  • J. Testa, A. Bellacosa
  • Biology, Medicine
    Proceedings of the National Academy of Sciences…
  • 25 September 2001
This issue of PNAS, Mayo and Donner report on yet another function of AKT, involving regulation of the Mdm2/p53 pathway, and define a family of closely related, highly conserved cellular homologues.
Germline BAP1 mutations predispose to malignant mesothelioma
A BAP1-related cancer syndrome is identified that is characterized by mesothelioma and uveal melanoma, and it is hypothesized that other cancers may also be involved and that mesot helioma predominates upon asbestos exposure.
Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2
A novel interactor is identified, designated APPL, which contains a pleckstrin homology (PH) domain, a phosphotyrosine binding (PTB) domain and a leucine zipper, classes of motifs defined in signaling molecules as functional interaction domains with specific targets.
AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas.
It is concluded thatAKT2 belongs to a distinct subfamily of protein-serine/threonine kinases containing Src homology 2-like domains and that alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas.
Frequent activation of AKT in non-small cell lung carcinomas and preneoplastic bronchial lesions.
Data suggest that AKT activation is a frequent and early event in lung tumorigenesis, which may enhance risk of progression to malignancy and represent a potentially important target for chemoprevention in individuals at high risk of NSCLC.