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Publication : A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations.

First Author  Zhang Y Year  2017
Journal  Cancer Cell Volume  31
Issue  6 Pages  820-832.e3
PubMed ID  28528867 Mgi Jnum  J:242567
Mgi Id  MGI:5905677 Doi  10.1016/j.ccell.2017.04.013
Citation  Zhang Y, et al. (2017) A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell 31(6):820-832.e3
abstractText  Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets. In addition to mutation, structural variations and partial copy losses involving PTEN and STK11 showed evidence for having functional relevance. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.
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