<br>癌症基因组图谱中的致癌信号通路。,Cell

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癌症基因组图谱中的致癌信号通路。
Cell ( IF 45.5 ) Pub Date : 2018-Apr-05 , DOI: 10.1016/j.cell.2018.03.035
Francisco Sanchez-Vega ₁ , Marco Mina ₂ , Joshua Armenia ₁ , Walid K Chatila ₃ , Augustin Luna ₄ , Konnor C La ₃ , Sofia Dimitriadoy ₅ , David L Liu ₆ , Havish S Kantheti ₇ , Sadegh Saghafinia ₂ , Debyani Chakravarty ₃ , Foysal Daian ₃ , Qingsong Gao ₈ , Matthew H Bailey ₈ , Wen-Wei Liang ₈ , Steven M Foltz ₈ , Ilya Shmulevich ₉ , Li Ding ₁₀ , Zachary Heins ₃ , Angelica Ochoa ₃ , Benjamin Gross ₃ , Jianjiong Gao ₃ , Hongxin Zhang ₃ , Ritika Kundra ₃ , Cyriac Kandoth ₃ , Istemi Bahceci ₁₁ , Leonard Dervishi ₁₁ , Ugur Dogrusoz ₁₁ , Wanding Zhou ₁₂ , Hui Shen ₁₂ , Peter W Laird ₁₂ , Gregory P Way ₁₃ , Casey S Greene ₁₃ , Han Liang ₁₄ , Yonghong Xiao ₁₅ , Chen Wang ₁₆ , Antonio Iavarone ₁₇ , Alice H Berger ₁₈ , Trever G Bivona ₁₉ , Alexander J Lazar ₂₀ , Gary D Hammer ₂₁ , Thomas Giordano ₂₂ , Lawrence N Kwong ₂₃ , Grant McArthur ₂₄ , Chenfei Huang ₂₅ , Aaron D Tward ₂₆ , Mitchell J Frederick ₂₅ , Frank McCormick ₂₇ , Matthew Meyerson ₆ , , Eliezer M Van Allen ₆ , Andrew D Cherniack ₆ , Giovanni Ciriello ₂ , Chris Sander ₄ , Nikolaus Schultz ₂₈

Affiliation

Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Department of Computational Biology, University of Lausanne (UNIL), 1011 Lausanne, Vaud, Switzerland and Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
cBio Center, Dana-Farber Cancer Institute, Boston, MA; Department of Cell Biology, Harvard Medical School, Boston, MA.
Princeton University, Princeton, NJ, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, US.
University of Texas at Dallas, Richardson, TX 75080, USA.
Department of Medicine and McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri, 63110, USA.
Institute for Systems Biology, Seattle, WA, USA.
Department of Medicine and McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri, 63110, USA; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
Computer Engineering Department, Bilkent University, Ankara 06800, Turkey.
Van Andel Research Institute, 333 Bostwick Ave NE, Grand Rapids Michigan, 49503, USA.
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
TESARO Inc., Waltham, MA, 02451, USA.
Department of Health Sciences Research and Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
Institute for Cancer Genetics, Department of Neurology and Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, California 94143, USA.
Departments of Pathology, Genomic Medicine & Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd-Unit 85, Houston, Texas 77030, USA.
Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, Endocrine Oncology Program, University of Michigan, Ann Arbor, Michigan, MI 48105, USA.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI; Department of Internal Medicine, Division of Metabolism, Endocrinology & Diabetes, University of Michigan Medical School, Ann Arbor, MI; Comprehensive Cancer Center, Michigan Medicine, Ann Arbor, MI, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; University of Melbourne, Melbourne, VIC, Australia.
Dept. of Otolaryngology, Baylor College of Medicine, USA.
University of California, San Francisco Department of Otolaryngology-Head and Neck Surgery. 2233 Post Street, San Francisco, CA, 94143, USA.
UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1450 3rd Street, San Francisco, CA 94143, USA.
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Departments of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

控制细胞周期进程、细胞凋亡和细胞生长的信号通路中的遗传改变是癌症的常见标志，但这些通路改变的程度、机制和同时发生因个体肿瘤和肿瘤类型而异。利用癌症基因组图谱 (TCGA) 分析的 9,125 个肿瘤中的突变、拷贝数变化、mRNA 表达、基因融合和 DNA 甲基化，我们分析了 10 个典型途径中体细胞改变的机制和模式：细胞周期、Hippo、Myc、 Notch、Nrf2、PI-3-激酶/Akt、RTK-RAS、TGFβ 信号传导、p53 和 β-连环蛋白/Wnt。我们绘制了 33 种癌症类型中通路改变的详细情况，分为 64 种亚型，并确定了共存和相互排斥的模式。 89% 的肿瘤在这些通路中至少有一种驱动改变，57% 的肿瘤至少有一种当前可用药物可能靶向的改变。百分之三十的肿瘤有多个可靶向的改变，表明有联合治疗的机会。

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更新日期：2018-04-06

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