Oncogenic signaling pathways in the Cancer Genome Atlas

buir.contributor.authorDoğrusöz, Uğur
dc.citation.epage337en_US
dc.citation.issueNumber2en_US
dc.citation.spage321en_US
dc.citation.volumeNumber173en_US
dc.contributor.authorSanchez-Vega, F.en_US
dc.contributor.authorMina, M.en_US
dc.contributor.authorArmenia, J.en_US
dc.contributor.authorChatila, W. K.en_US
dc.contributor.authorLuna, A.en_US
dc.contributor.authorLa, K. C.en_US
dc.contributor.authorDimitriadoy, S.en_US
dc.contributor.authorLiu, D. L.en_US
dc.contributor.authorKantheti, H. S.en_US
dc.contributor.authorSaghafinia, S.en_US
dc.contributor.authorChakravarty, D.en_US
dc.contributor.authorDaian, F.en_US
dc.contributor.authorGao, Q.en_US
dc.contributor.authorBailey, M. H.en_US
dc.contributor.authorLiang, W. -W.en_US
dc.contributor.authorFoltz, S. M.en_US
dc.contributor.authorShmulevich, I.en_US
dc.contributor.authorDing, L.en_US
dc.contributor.authorHeins, Z.en_US
dc.contributor.authorOchoa, A.en_US
dc.contributor.authorGross, B.en_US
dc.contributor.authorGao, J.en_US
dc.contributor.authorZhang, H.en_US
dc.contributor.authorKundra, R.en_US
dc.contributor.authorKandoth, C.en_US
dc.contributor.authorBahceci, I.en_US
dc.contributor.authorDervishi, L.en_US
dc.contributor.authorDoğrusöz, Uğuren_US
dc.contributor.authorZhou, W.en_US
dc.contributor.authorShen, H.en_US
dc.contributor.authorLaird, P. W.en_US
dc.contributor.authorWay, G. P.en_US
dc.contributor.authorGreene, C. S.en_US
dc.contributor.authorLiang, H.en_US
dc.contributor.authorXiao, Y.en_US
dc.contributor.authorWang, C.en_US
dc.contributor.authorIavarone, A.en_US
dc.contributor.authorBerger, A. H.en_US
dc.contributor.authorBivona, T. G.en_US
dc.contributor.authorLazar, A. J.en_US
dc.contributor.authorHammer, G. D.en_US
dc.contributor.authorGiordano, T.en_US
dc.contributor.authorKwong, L. N.en_US
dc.contributor.authorMcArthur, G.en_US
dc.contributor.authorHuang, C.en_US
dc.contributor.authorTward, A. D.en_US
dc.contributor.authorFrederick, M. J.en_US
dc.contributor.authorMcCormick, F.en_US
dc.contributor.authorMeyerson, M.en_US
dc.contributor.authorCaesar-Johnson, S. J.en_US
dc.contributor.authorDemchok, J. A.en_US
dc.contributor.authorFelau, I.en_US
dc.contributor.authorKasapi, M.en_US
dc.contributor.authorFerguson, M. L.en_US
dc.contributor.authorHutter, C. M.en_US
dc.contributor.authorSofia, H. J.en_US
dc.contributor.authorTarnuzzer, R.en_US
dc.contributor.authorWang, Z.en_US
dc.contributor.authorYang, L.en_US
dc.contributor.authorZenklusen, J. C.en_US
dc.contributor.authorZhang, J. J.en_US
dc.contributor.authorChudamani, S.en_US
dc.contributor.authorLiu, J.en_US
dc.contributor.authorLolla, L.en_US
dc.contributor.authorNaresh, R.en_US
dc.contributor.authorPihl, T.en_US
dc.contributor.authorSun, Q.en_US
dc.contributor.authorWan, Y.en_US
dc.contributor.authorWu, Y.en_US
dc.contributor.authorCho, J.en_US
dc.contributor.authorDeFreitas, T.en_US
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dc.contributor.authorGetz, G.en_US
dc.contributor.authorHeiman, D. I.en_US
dc.contributor.authorKim, J.en_US
dc.contributor.authorLawrence, M. S.en_US
dc.contributor.authorLin, P.en_US
dc.contributor.authorMeier, S.en_US
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dc.contributor.authorZhang, H.en_US
dc.contributor.authorBernard, B.en_US
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dc.contributor.authorLeinonen, K.en_US
dc.contributor.authorLiu, Y.en_US
dc.contributor.authorMiller, M.en_US
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dc.contributor.authorShmulevich, I.en_US
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dc.contributor.authorAkbani, R.en_US
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dc.contributor.authorJu, Z.en_US
dc.contributor.authorKanchi, R. S.en_US
dc.contributor.authorKorkut, A.en_US
dc.contributor.authorLi, J.en_US
dc.contributor.authorLiang, H.en_US
dc.contributor.authorLing, S.en_US
dc.contributor.authorLiu W.en_US
dc.contributor.authorLu, Y.en_US
dc.contributor.authorMills, G. B.en_US
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dc.contributor.authorRao, A.en_US
dc.contributor.authorRyan, M.en_US
dc.contributor.authorWang, J.en_US
dc.contributor.authorWeinstein, J. N.en_US
dc.contributor.authorZhang, J.en_US
dc.contributor.authorAbeshouse, A.en_US
dc.contributor.authorArmenia, J.en_US
dc.contributor.authorChakravarty, D.en_US
dc.contributor.authorChatila, W. K.en_US
dc.contributor.authorde, Bruijn, I.en_US
dc.contributor.authorGao, J.en_US
dc.contributor.authorGross, B. E.en_US
dc.contributor.authorHeins, Z. J.en_US
dc.contributor.authorKundra, R.en_US
dc.contributor.authorLa, K.en_US
dc.contributor.authorLadanyi, M.en_US
dc.contributor.authorLuna, A.en_US
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dc.contributor.authorZhang, H.en_US
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dc.contributor.authorBenz, C.en_US
dc.contributor.authorStuart, J. M.en_US
dc.contributor.authorWong, C. K.en_US
dc.contributor.authorYau, C.en_US
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dc.contributor.authorBalasundaram, M.en_US
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dc.contributor.authorBrooks, D.en_US
dc.contributor.authorCarlsen, R.en_US
dc.contributor.authorChuah, E.en_US
dc.contributor.authorDhalla, N.en_US
dc.contributor.authorHolt, R.en_US
dc.contributor.authorJones, S. J. M.en_US
dc.contributor.authorKasaian, K.en_US
dc.contributor.authorLee, D.en_US
dc.contributor.authorMa, Y.en_US
dc.contributor.authorMarra, M. A.en_US
dc.contributor.authorMayo, M.en_US
dc.contributor.authorMoore, R. A.en_US
dc.contributor.authorMungall, A. J.en_US
dc.contributor.authorMungall, K.en_US
dc.contributor.authorRobertson, A. G.en_US
dc.contributor.authorSadeghi, S.en_US
dc.contributor.authorSchein, J. E.en_US
dc.contributor.authorSipahimalani, P.en_US
dc.contributor.authorTam, A.en_US
dc.contributor.authorThiessen, N.en_US
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dc.contributor.authorWong, T.en_US
dc.contributor.authorBerger, A. C.en_US
dc.contributor.authorBeroukhim, R.en_US
dc.contributor.authorCherniack, A. D.en_US
dc.contributor.authorCibulskis, C.en_US
dc.contributor.authorGabriel, S. B.en_US
dc.contributor.authorGao, G. F.en_US
dc.contributor.authorHa, G.en_US
dc.contributor.authorMeyerson, M.en_US
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dc.contributor.authorHeath, S.en_US
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dc.contributor.authorVan, Tine, B.en_US
dc.contributor.authorWestervelt, P.en_US
dc.contributor.authorRubin, M. A.en_US
dc.contributor.authorLee, J. I.en_US
dc.contributor.authorAredes, N. D.en_US
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dc.contributor.authorVan, Allen, E. M.en_US
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dc.contributor.authorThe, Cancer, Genome, Atlas, Research, Network.tifen_US
dc.date.accessioned2019-02-21T16:01:26Z
dc.date.available2019-02-21T16:01:26Z
dc.date.issued2018en_US
dc.departmentDepartment of Computer Engineeringen_US
dc.description.abstractGenetic 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. An integrated analysis of genetic alterations in 10 signaling pathways in >9,000 tumors profiled by TCGA highlights significant representation of individual and co-occurring actionable alterations in these pathways, suggesting opportunities for targeted and combination therapies.
dc.description.provenanceMade available in DSpace on 2019-02-21T16:01:26Z (GMT). No. of bitstreams: 1 Bilkent-research-paper.pdf: 222869 bytes, checksum: 842af2b9bd649e7f548593affdbafbb3 (MD5) Previous issue date: 2018en
dc.description.sponsorshipMichael Seiler, Peter G. Smith, Ping Zhu, Silvia Buonamici, and Lihua Yu are employees of H3 Biomedicine, Inc. Parts of this work are the subject of a patent application: WO2017040526 titled “Splice variants associated with neomorphic sf3b1 mutants.” Shouyoung Peng, Anant A. Agrawal, James Palacino, and Teng Teng are employees of H3 Biomedicine, Inc. Andrew D. Cherniack, Ashton C. Berger, and Galen F. Gao receive research support from Bayer Pharmaceuticals. Gordon B. Mills serves on the External Scientific Review Board of Astrazeneca. Anil Sood is on the Scientific Advisory Board for Kiyatec and is a shareholder in BioPath. Jonathan S. Serody receives funding from Merck, Inc. Kyle R. Covington is an employee of Castle Biosciences, Inc. Preethi H. Gunaratne is founder, CSO, and shareholder of NextmiRNA Therapeutics. Christina Yau is a part-time employee/consultant at NantOmics. Franz X. Schaub is an employee and shareholder of SEngine Precision Medicine, Inc. Carla Grandori is an employee, founder, and shareholder of SEngine Precision Medicine, Inc. Robert N. Eisenman is a member of the Scientific Advisory Boards and shareholder of Shenogen Pharma and Kronos Bio. Daniel J. Weisenberger is a consultant for Zymo Research Corporation. Joshua M. Stuart is the founder of Five3 Genomics and shareholder of NantOmics. Marc T. Goodman receives research support from Merck, Inc. Andrew J. Gentles is a consultant for Cibermed. Charles M. Perou is an equity stock holder, consultant, and Board of Directors member of BioClassifier and GeneCentric Diagnostics and is also listed as an inventor on patent applications on the Breast PAM50 and Lung Cancer Subtyping assays. Matthew Meyerson receives research support from Bayer Pharmaceuticals; is an equity holder in, consultant for, and Scientific Advisory Board chair for OrigiMed; and is an inventor of a patent for EGFR mutation diagnosis in lung cancer, licensed to LabCorp. Eduard Porta-Pardo is an inventor of a patent for domainXplorer. Han Liang is a shareholder and scientific advisor of Precision Scientific and Eagle Nebula. Da Yang is an inventor on a pending patent application describing the use of antisense oligonucleotides against specific lncRNA sequence as diagnostic and therapeutic tools. Yonghong Xiao was an employee and shareholder of TESARO, Inc. Bin Feng is an employee and shareholder of TESARO, Inc. Carter Van Waes received research funding for the study of IAP inhibitor ASTX660 through a Cooperative Agreement between NIDCD, NIH, and Astex Pharmaceuticals. Raunaq Malhotra is an employee and shareholder of Seven Bridges, Inc. Peter W. Laird serves on the Scientific Advisory Board for AnchorDx. Joel Tepper is a consultant at EMD Serono. Kenneth Wang serves on the Advisory Board for Boston Scientific, Microtech, and Olympus. Andrea Califano is a founder, shareholder, and advisory board member of DarwinHealth, Inc. and a shareholder and advisory board member of Tempus, Inc. Toni K. Choueiri serves as needed on advisory boards for Bristol-Myers Squibb, Merck, and Roche. Lawrence Kwong receives research support from Array BioPharma. Sharon E. Plon is a member of the Scientific Advisory Board for Baylor Genetics Laboratory. Beth Y. Karlan serves on the Advisory Board of Invitae.
dc.identifier.doi10.1016/j.cell.2018.03.035en_US
dc.identifier.eissn1875-9777en_US
dc.identifier.issn0092-8674en_US
dc.identifier.urihttp://hdl.handle.net/11693/49844en_US
dc.language.isoEnglishen_US
dc.publisherCell Pressen_US
dc.relation.isversionofhttps://doi.org/10.1016/j.cell.2018.03.035
dc.relation.projectU24 CA143845, U24 CA143866, U54 HG003273, U24 CA143848, U24 CA143835, U54 HG003067, U24 CA143843, U24 CA143883, U24 CA143867, U24 CA144025, U24 CA143799, P30 CA016672, U24 CA143840, U24 CA143882, U24 CA143858, U54 HG003079 - Diagnostics - Baylor University - Olympus - Bristol-Myers Squibb, BMS - Chief Scientist Office, CSO - National Institutes of Health, NIH - Roche - Array BioPharma - AstraZeneca - National Institute on Deafness and Other Communication Disorders, NIDCD - Merck - EMD Serono
dc.rightsinfo:eu-repo/semantics/openAccess
dc.source.titleCellen_US
dc.subjectCancer genome atlasen_US
dc.subjectCancer genomicsen_US
dc.subjectCombination therapyen_US
dc.subjectPan-canceren_US
dc.subjectPanCanAtlasen_US
dc.subjectPrecision oncologyen_US
dc.subjectSignaling pathwaysen_US
dc.subjectTCGAen_US
dc.subjectTherapeuticsen_US
dc.subjectWhole exome sequencingen_US
dc.titleOncogenic signaling pathways in the Cancer Genome Atlasen_US
dc.typeArticleen_US

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