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A Pan-Cancer Analysis Reveals High-Frequency Genetic Alterations in Mediators of Signaling by the TGF-ß Superfamily.
Korkut, Anil; Zaidi, Sobia; Kanchi, Rupa S; Rao, Shuyun; Gough, Nancy R; Schultz, Andre; Li, Xubin; Lorenzi, Philip L; Berger, Ashton C; Robertson, Gordon; Kwong, Lawrence N; Datto, Mike; Roszik, Jason; Ling, Shiyun; Ravikumar, Visweswaran; Manyam, Ganiraju; Rao, Arvind; Shelley, Simon; Liu, Yuexin; Ju, Zhenlin; Hansel, Donna; de Velasco, Guillermo; Pennathur, Arjun; Andersen, Jesper B; O'Rourke, Colm J; Ohshiro, Kazufumi; Jogunoori, Wilma; Nguyen, Bao-Ngoc; Li, Shulin; Osmanbeyoglu, Hatice U; Ajani, Jaffer A; Mani, Sendurai A; Houseman, Andres; Wiznerowicz, Maciej; Chen, Jian; Gu, Shoujun; Ma, Wencai; Zhang, Jiexin; Tong, Pan; Cherniack, Andrew D; Deng, Chuxia; Resar, Linda; Weinstein, John N; Mishra, Lopa; Akbani, Rehan.
Afiliação
  • Korkut A; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zaidi S; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Kanchi RS; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Rao S; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Gough NR; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Schultz A; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Li X; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Lorenzi PL; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Berger AC; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Robertson G; Canada's Michael Smith Genome Sciences Center, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.
  • Kwong LN; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Datto M; Department of Pathology, Duke School of Medicine Durham, Durham, NC 27710, USA.
  • Roszik J; Department of Melanoma Medical Oncology and Genomic Medicine, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ling S; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ravikumar V; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Manyam G; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Rao A; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Shelley S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
  • Liu Y; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Ju Z; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Hansel D; Department of Pathology, University of California, San Diego, La Jolla, CA 92093, 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.
  • Pennathur A; Department of Cardiothoracic Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
  • Andersen JB; Department of Health and Medical Sciences, Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • O'Rourke CJ; Department of Health and Medical Sciences, Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaloes Vej 5, Copenhagen 2200, Denmark.
  • Ohshiro K; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Jogunoori W; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA; Veterans Affairs Medical Center, Institute of Clinical Research, Washington, DC 20422, USA.
  • Nguyen BN; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Li S; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Osmanbeyoglu HU; Memorial Sloan Kettering Cancer Center, Computational & Systems Biology Program, New York, NY 10065, USA.
  • Ajani JA; Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mani SA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Houseman A; College of Public Health and Human Sciences, Oregon State University, Corvallis, OR 9733, USA.
  • Wiznerowicz M; Poznan University of Medical Sciences, Poznan 61701, Poland; Greater Poland Cancer Center, Poznan 61866, Poland; International Institute for Molecular Oncology, Poznan 60203, Poland.
  • Chen J; Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Gu S; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA.
  • Ma W; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Zhang J; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Tong P; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Cherniack AD; Cancer Program, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
  • Deng C; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA; Faculty of Health Sciences, University of Macau, Macau, Macau SAR, China.
  • Resar L; Departments of Medicine, Division of Hematology, Oncology and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Weinstein JN; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, MD Anderson Cancer Center, Houston, TX 77030, USA.
  • Mishra L; Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC 20037, USA; Veterans Affairs Medical Center, Institute of Clinical Research, Washington, DC 20422, USA. Electronic address: lopamishra2@gmail.com.
  • Akbani R; Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: rakbani@mdanderson.org.
Cell Syst ; 7(4): 422-437.e7, 2018 10 24.
Article em En | MEDLINE | ID: mdl-30268436
ABSTRACT
We present an integromic analysis of gene alterations that modulate transforming growth factor ß (TGF-ß)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-ß signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-ß ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-ß superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-ß signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-ß superfamily.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator de Crescimento Transformador beta / Taxa de Mutação / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Syst Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Fator de Crescimento Transformador beta / Taxa de Mutação / Neoplasias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Syst Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos