| Literature DB >> 28528867 |
Yiqun Zhang1, Patrick Kwok-Shing Ng2, Melanie Kucherlapati3, Fengju Chen1, Yuexin Liu4, Yiu Huen Tsang5, Guillermo de Velasco6, Kang Jin Jeong7, Rehan Akbani4, Angela Hadjipanayis3, Angeliki Pantazi8, Christopher A Bristow9, Eunjung Lee3, Harshad S Mahadeshwar9, Jiabin Tang9, Jianhua Zhang9, Lixing Yang10, Sahil Seth9, Semin Lee10, Xiaojia Ren8, Xingzhi Song9, Huandong Sun9, Jonathan Seidman11, Lovelace J Luquette10, Ruibin Xi10, Lynda Chin12, Alexei Protopopov13, Thomas F Westbrook14, Carl Simon Shelley15, Toni K Choueiri16, Michael Ittmann17, Carter Van Waes18, John N Weinstein4, Han Liang19, Elizabeth P Henske20, Andrew K Godwin21, Peter J Park22, Raju Kucherlapati3, Kenneth L Scott5, Gordon B Mills23, David J Kwiatkowski24, Chad J Creighton25.
Abstract
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.Entities:
Keywords: PI3K/AKT/mTOR pathway; The Cancer Genome Atlas; integrative genomics analysis; pan-cancer analysis; proteomics; reverse-phase protein arrays
Mesh：
Substances：
Year: 2017 PMID： 28528867 PMCID： PMC5502825 DOI： 10.1016/j.ccell.2017.04.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743