| Literature DB >> 29625050 |
Francisco Sanchez-Vega1, Marco Mina2, Joshua Armenia1, Walid K Chatila3, Augustin Luna4, Konnor C La3, Sofia Dimitriadoy5, David L Liu6, Havish S Kantheti7, Sadegh Saghafinia2, Debyani Chakravarty3, Foysal Daian3, Qingsong Gao8, Matthew H Bailey8, Wen-Wei Liang8, Steven M Foltz8, Ilya Shmulevich9, Li Ding10, Zachary Heins3, Angelica Ochoa3, Benjamin Gross3, Jianjiong Gao3, Hongxin Zhang3, Ritika Kundra3, Cyriac Kandoth3, Istemi Bahceci11, Leonard Dervishi11, Ugur Dogrusoz11, Wanding Zhou12, Hui Shen12, Peter W Laird12, Gregory P Way13, Casey S Greene13, Han Liang14, Yonghong Xiao15, Chen Wang16, Antonio Iavarone17, Alice H Berger18, Trever G Bivona19, Alexander J Lazar20, Gary D Hammer21, Thomas Giordano22, Lawrence N Kwong23, Grant McArthur24, Chenfei Huang25, Aaron D Tward26, Mitchell J Frederick25, Frank McCormick27, Matthew Meyerson6, Eliezer M Van Allen6, Andrew D Cherniack6, Giovanni Ciriello28, Chris Sander29, Nikolaus Schultz30.
Abstract
Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFβ signaling, p53 and β-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.Entities:
Keywords: PanCanAtlas; TCGA; cancer genome atlas; cancer genomics; combination therapy; pan-cancer; precision oncology; signaling pathways; therapeutics; whole exome sequencing
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Year: 2018 PMID： 29625050 PMCID： PMC6070353 DOI： 10.1016/j.cell.2018.03.035
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582