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

TitleA Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations.
Publication TypeJournal Article
Year of Publication2017
AuthorsZhang, Y, Ng, PKwok-Shing, Kucherlapati, M, Chen, F, Liu, Y, Tsang, YHuen, De Velasco, G, Jeong, KJin, Akbani, R, Hadjipanayis, A, Pantazi, A, Bristow, CA, Lee, E, Mahadeshwar, HS, Tang, J, Zhang, J, Yang, L, Seth, S, Lee, S, Ren, X, Song, X, Sun, H, Seidman, J, Luquette, LJ, Xi, R, Chin, L, Protopopov, A, Westbrook, TF, Shelley, CSimon, Choueiri, TK, Ittmann, M, Van Waes, C, Weinstein, JN, Liang, H, Henske, EP, Godwin, AK, Park, PJ, Kucherlapati, R, Scott, KL, Mills, GB, Kwiatkowski, DJ, Creighton, CJ
JournalCancer Cell
Volume31
Issue6
Pagination820-832.e3
Date Published2017 Jun 12
ISSN1878-3686
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.

DOI10.1016/j.ccell.2017.04.013
Alternate JournalCancer Cell
PubMed ID28528867
PubMed Central IDPMC5502825
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
P50 CA101942 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
P01 CA120964 / CA / NCI NIH HHS / United States
P50 CA098258 / CA / NCI NIH HHS / United States
U01 CA168394 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
R01 CA175486 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
R21 CA191687 / CA / NCI NIH HHS / United States
U24 CA209851 / CA / NCI NIH HHS / United States