@article {1109301, title = {A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations}, journal = {Cancer Cell}, volume = {31}, number = {6}, year = {2017}, month = {2017 Jun 12}, pages = {820-832.e3}, 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.}, issn = {1878-3686}, doi = {10.1016/j.ccell.2017.04.013}, author = {Zhang, Yiqun and Kwok-Shing Ng, Patrick and Kucherlapati, Melanie and Chen, Fengju and Liu, Yuexin and Tsang, Yiu Huen and De Velasco, Guillermo and Jeong, Kang Jin and Akbani, Rehan and Hadjipanayis, Angela and Pantazi, Angeliki and Bristow, Christopher A and Lee, Eunjung and Mahadeshwar, Harshad S and Tang, Jiabin and Zhang, Jianhua and Yang, Lixing and Seth, Sahil and Lee, Semin and Ren, Xiaojia and Song, Xingzhi and Sun, Huandong and Seidman, Jonathan and Luquette, Lovelace J and Xi, Ruibin and Chin, Lynda and Protopopov, Alexei and Westbrook, Thomas F and Shelley, Carl Simon and Choueiri, Toni K and Ittmann, Michael and Van Waes, Carter and Weinstein, John N and Liang, Han and Henske, Elizabeth P and Godwin, Andrew K and Park, Peter J and Kucherlapati, Raju and Scott, Kenneth L and Mills, Gordon B and Kwiatkowski, David J and Creighton, Chad J} }