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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 B; Kwiatkowski, David J; Creighton, Chad J.
Afiliação
  • Zhang Y; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Kwok-Shing Ng P; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Kucherlapati M; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Chen F; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Liu Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tsang YH; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • de Velasco G; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid 28041, Spain.
  • Jeong KJ; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
  • Akbani R; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hadjipanayis A; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Pantazi A; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; KEW Inc., Cambridge, MA 02139, USA.
  • Bristow CA; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lee E; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Mahadeshwar HS; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tang J; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang J; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Yang L; Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Seth S; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lee S; Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Ren X; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; KEW Inc., Cambridge, MA 02139, USA.
  • Song X; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Sun H; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Seidman J; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Luquette LJ; Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Xi R; Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
  • Chin L; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University Cambridge, Cambridge, MA 02142, USA.
  • Protopopov A; Department of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; KEW Inc., Cambridge, MA 02139, USA.
  • Westbrook TF; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shelley CS; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
  • Choueiri TK; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
  • Ittmann M; Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
  • Van Waes C; Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
  • Weinstein JN; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Liang H; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
  • Henske EP; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02142, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
  • Godwin AK; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
  • Park PJ; Center for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Kucherlapati R; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Scott KL; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Mills GB; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: gmills@mdanderson.org.
  • Kwiatkowski DJ; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02142, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. Electronic address: dkwiatkowski@rics.bwh.harvard.edu.
  • Creighton CJ; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
Cancer Cell ; 31(6): 820-832.e3, 2017 06 12.
Article em En | MEDLINE | ID: mdl-28528867
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Serina-Treonina Quinases TOR / Proteogenômica / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfatidilinositol 3-Quinases / Proteínas Proto-Oncogênicas c-akt / Serina-Treonina Quinases TOR / Proteogenômica / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2017 Tipo de documento: Article