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 language | English (US) |
|---|---|
| Pages (from-to) | 820-832.e3 |
| Journal | Cancer Cell |
| Volume | 31 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 12 2017 |
| Externally published | Yes |
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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
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 journal › Article
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TY - JOUR
T1 - A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations
AU - Zhang, Yiqun
AU - Kwok-Shing Ng, Patrick
AU - Kucherlapati, Melanie
AU - Chen, Fengju
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.
PY - 2017/6/12
Y1 - 2017/6/12
N2 - 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.
AB - 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.
KW - integrative genomics analysis
KW - pan-cancer analysis
KW - PI3K/AKT/mTOR pathway
KW - proteomics
KW - reverse-phase protein arrays
KW - The Cancer Genome Atlas
UR - http://www.scopus.com/inward/record.url?scp=85019369051&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019369051&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2017.04.013
DO - 10.1016/j.ccell.2017.04.013
M3 - Article
C2 - 28528867
AN - SCOPUS:85019369051
VL - 31
SP - 820-832.e3
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 6
ER -