Title |
A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
|
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Published in |
Cancer Cell, May 2017
|
DOI | 10.1016/j.ccell.2017.04.013 |
Pubmed ID | |
Authors |
Yiqun Zhang, Patrick Kwok-Shing Ng, Melanie Kucherlapati, Fengju Chen, Yuexin Liu, Yiu Huen Tsang, Guillermo de Velasco, Kang Jin Jeong, Rehan Akbani, Angela Hadjipanayis, Angeliki Pantazi, Christopher A. Bristow, Eunjung Lee, Harshad S. Mahadeshwar, Jiabin Tang, Jianhua Zhang, Lixing Yang, Sahil Seth, Semin Lee, Xiaojia Ren, Xingzhi Song, Huandong Sun, Jonathan Seidman, Lovelace J. Luquette, Ruibin Xi, Lynda Chin, Alexei Protopopov, Thomas F. Westbrook, Carl Simon Shelley, Toni K. Choueiri, Michael Ittmann, Carter Van Waes, John N. Weinstein, Han Liang, Elizabeth P. Henske, Andrew K. Godwin, Peter J. Park, Raju Kucherlapati, Kenneth L. Scott, Gordon B. Mills, David J. Kwiatkowski, Chad J. Creighton |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 47 | 27% |
Canada | 9 | 5% |
United Kingdom | 8 | 5% |
Spain | 6 | 3% |
France | 5 | 3% |
Australia | 5 | 3% |
Sweden | 3 | 2% |
Germany | 3 | 2% |
Japan | 2 | 1% |
Other | 23 | 13% |
Unknown | 62 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 82 | 47% |
Scientists | 71 | 41% |
Practitioners (doctors, other healthcare professionals) | 15 | 9% |
Science communicators (journalists, bloggers, editors) | 5 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | <1% |
United Kingdom | 2 | <1% |
Brazil | 1 | <1% |
France | 1 | <1% |
Sweden | 1 | <1% |
Unknown | 459 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 100 | 21% |
Student > Ph. D. Student | 90 | 19% |
Student > Master | 38 | 8% |
Student > Bachelor | 29 | 6% |
Other | 20 | 4% |
Other | 68 | 15% |
Unknown | 121 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 153 | 33% |
Agricultural and Biological Sciences | 67 | 14% |
Medicine and Dentistry | 60 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 12 | 3% |
Computer Science | 8 | 2% |
Other | 37 | 8% |
Unknown | 129 | 28% |