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

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 RenXingzhi 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 Mills, David J. Kwiatkowski, Chad J. Creighton

Research output: Contribution to journalArticle

86 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)820-832.e3
JournalCancer Cell
Volume31
Issue number6
DOIs
StatePublished - Jun 12 2017
Externally publishedYes

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Atlases
Phosphatidylinositol 3-Kinases
Mutation
Neoplasms
Gene Frequency
Computer Simulation
RNA
Proteogenomics
Proteins

Keywords

  • integrative genomics analysis
  • pan-cancer analysis
  • PI3K/AKT/mTOR pathway
  • proteomics
  • reverse-phase protein arrays
  • The Cancer Genome Atlas

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Zhang, Y., Kwok-Shing Ng, P., Kucherlapati, M., Chen, F., Liu, Y., Tsang, Y. H., ... Creighton, C. J. (2017). A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell, 31(6), 820-832.e3. https://doi.org/10.1016/j.ccell.2017.04.013

A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. / Zhang, Yiqun; Kwok-Shing Ng, Patrick; Kucherlapati, Melanie; Chen, Fengju; Liu, Yuexin; Tsang, Yiu Huen; de Velasco, Guillermo; Jeong, Kang Jin; Akbani, Rehan; Hadjipanayis, Angela; Pantazi, Angeliki; Bristow, Christopher A.; Lee, Eunjung; Mahadeshwar, Harshad S.; Tang, Jiabin; Zhang, Jianhua; Yang, Lixing; Seth, Sahil; Lee, Semin; Ren, Xiaojia; Song, Xingzhi; Sun, Huandong; Seidman, Jonathan; Luquette, Lovelace J.; Xi, Ruibin; Chin, Lynda; Protopopov, Alexei; Westbrook, Thomas F.; Shelley, Carl Simon; Choueiri, Toni K.; Ittmann, Michael; Van Waes, Carter; Weinstein, John N.; Liang, Han; Henske, Elizabeth P.; Godwin, Andrew K.; Park, Peter J.; Kucherlapati, Raju; Scott, Kenneth L.; Mills, Gordon; Kwiatkowski, David J.; Creighton, Chad J.

In: Cancer Cell, Vol. 31, No. 6, 12.06.2017, p. 820-832.e3.

Research output: Contribution to journalArticle

Zhang, Y, Kwok-Shing Ng, P, Kucherlapati, M, Chen, F, Liu, Y, Tsang, YH, de Velasco, G, Jeong, KJ, 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, CS, Choueiri, TK, Ittmann, M, Van Waes, C, Weinstein, JN, Liang, H, Henske, EP, Godwin, AK, Park, PJ, Kucherlapati, R, Scott, KL, Mills, G, Kwiatkowski, DJ & Creighton, CJ 2017, 'A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations', Cancer Cell, vol. 31, no. 6, pp. 820-832.e3. https://doi.org/10.1016/j.ccell.2017.04.013
Zhang Y, Kwok-Shing Ng P, Kucherlapati M, Chen F, Liu Y, Tsang YH et al. A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. Cancer Cell. 2017 Jun 12;31(6):820-832.e3. https://doi.org/10.1016/j.ccell.2017.04.013
Zhang, Yiqun ; Kwok-Shing Ng, Patrick ; Kucherlapati, Melanie ; Chen, Fengju ; Liu, Yuexin ; Tsang, Yiu Huen ; de Velasco, Guillermo ; Jeong, Kang Jin ; Akbani, Rehan ; Hadjipanayis, Angela ; Pantazi, Angeliki ; Bristow, Christopher A. ; Lee, Eunjung ; Mahadeshwar, Harshad S. ; Tang, Jiabin ; Zhang, Jianhua ; Yang, Lixing ; Seth, Sahil ; Lee, Semin ; Ren, Xiaojia ; Song, Xingzhi ; Sun, Huandong ; Seidman, Jonathan ; Luquette, Lovelace J. ; Xi, Ruibin ; Chin, Lynda ; Protopopov, Alexei ; Westbrook, Thomas F. ; Shelley, Carl Simon ; Choueiri, Toni K. ; Ittmann, Michael ; Van Waes, Carter ; Weinstein, John N. ; Liang, Han ; Henske, Elizabeth P. ; Godwin, Andrew K. ; Park, Peter J. ; Kucherlapati, Raju ; Scott, Kenneth L. ; Mills, Gordon ; Kwiatkowski, David J. ; Creighton, Chad J. / A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations. In: Cancer Cell. 2017 ; Vol. 31, No. 6. pp. 820-832.e3.
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AU - Liu, Yuexin

AU - Tsang, Yiu Huen

AU - de Velasco, Guillermo

AU - Jeong, Kang Jin

AU - Akbani, Rehan

AU - Hadjipanayis, Angela

AU - Pantazi, Angeliki

AU - Bristow, Christopher A.

AU - Lee, Eunjung

AU - Mahadeshwar, Harshad S.

AU - Tang, Jiabin

AU - Zhang, Jianhua

AU - Yang, Lixing

AU - Seth, Sahil

AU - Lee, Semin

AU - Ren, Xiaojia

AU - Song, Xingzhi

AU - Sun, Huandong

AU - Seidman, Jonathan

AU - Luquette, Lovelace J.

AU - Xi, Ruibin

AU - Chin, Lynda

AU - Protopopov, Alexei

AU - Westbrook, Thomas F.

AU - Shelley, Carl Simon

AU - Choueiri, Toni K.

AU - Ittmann, Michael

AU - Van Waes, Carter

AU - Weinstein, John N.

AU - Liang, Han

AU - Henske, Elizabeth P.

AU - Godwin, Andrew K.

AU - Park, Peter J.

AU - Kucherlapati, Raju

AU - Scott, Kenneth L.

AU - Mills, Gordon

AU - Kwiatkowski, David J.

AU - Creighton, Chad J.

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