Journal article
Oncogenic Signaling Pathways in The Cancer Genome Atlas
Cell, Vol.173(2), pp.321-337.e10
04/05/2018
DOI: 10.1016/j.cell.2018.03.035
PMCID: PMC6070353
PMID: 29625050
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.
Details
- Title: Subtitle
- Oncogenic Signaling Pathways in The Cancer Genome Atlas
- Creators
- Francisco Sanchez-Vega - Memorial Sloan Kettering Cancer CenterMarco Mina - SIB Swiss Institute of BioinformaticsJoshua Armenia - Memorial Sloan Kettering Cancer CenterWalid K Chatila - Memorial Sloan Kettering Cancer CenterAugustin Luna - Harvard UniversityKonnor C La - Memorial Sloan Kettering Cancer CenterSofia Dimitriadoy - Princeton UniversityDavid L Liu - Harvard UniversityHavish S Kantheti - The University of Texas at DallasSadegh Saghafinia - SIB Swiss Institute of BioinformaticsDebyani Chakravarty - Memorial Sloan Kettering Cancer CenterFoysal Daian - Memorial Sloan Kettering Cancer CenterQingsong Gao - Washington University in St. LouisMatthew H Bailey - Washington University in St. LouisWen-Wei Liang - Washington University in St. LouisSteven M Foltz - Washington University in St. LouisIlya Shmulevich - Institute for Systems BiologyLi Ding - Washington University in St. LouisZachary Heins - Memorial Sloan Kettering Cancer CenterAngelica Ochoa - Memorial Sloan Kettering Cancer CenterBenjamin Gross - Memorial Sloan Kettering Cancer CenterJianjiong Gao - Memorial Sloan Kettering Cancer CenterHongxin Zhang - Memorial Sloan Kettering Cancer CenterRitika Kundra - Memorial Sloan Kettering Cancer CenterCyriac Kandoth - Memorial Sloan Kettering Cancer CenterIstemi Bahceci - Bilkent UniversityLeonard Dervishi - Bilkent UniversityUgur Dogrusoz - Bilkent UniversityWanding Zhou - Van Andel InstituteHui Shen - Van Andel InstitutePeter W Laird - Van Andel InstituteGregory P Way - University of PennsylvaniaCasey S Greene - University of PennsylvaniaHan Liang - The University of Texas MD Anderson Cancer CenterYonghong Xiao - TESARO Inc., Waltham, MA, 02451, USAChen Wang - Mayo ClinicAntonio Iavarone - University Medical CenterAlice H Berger - Cancer Research CenterTrever G Bivona - University of California, San FranciscoAlexander J Lazar - The University of Texas MD Anderson Cancer CenterGary D Hammer - University of MichiganThomas Giordano - University of Michigan Medical SchoolLawrence N Kwong - The University of Texas MD Anderson Cancer CenterGrant McArthur - Peter MacCallum Cancer CentreChenfei Huang - Baylor College of MedicineAaron D Tward - University of California, San FranciscoFrank McCormick - University of California, San FranciscoMitchell J Frederick - Baylor College of MedicineMatthew Meyerson - Harvard UniversityEliezer M Van Allen - Harvard UniversityAndrew D Cherniack - Harvard UniversityGiovanni Ciriello - SIB Swiss Institute of BioinformaticsChris Sander - Harvard UniversityNikolaus Schultz - Memorial Sloan Kettering Cancer Center
- Contributors
- Cancer Genome Atlas Research NetworkDeqin Ma - University of Iowa, PathologyMohammed M Milhem - University of Iowa, Internal MedicineAaron D Bossler (Contributor) - University of Iowa, Pathology
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.173(2), pp.321-337.e10
- DOI
- 10.1016/j.cell.2018.03.035
- PMID
- 29625050
- PMCID
- PMC6070353
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Grant note
- U24 CA143843 / NCI NIH HHS U24 CA210957 / NCI NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS U24 CA143883 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA143799 / NCI NIH HHS T32 HG000046 / NHGRI NIH HHS P41 GM103504 / NIGMS NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS P30 CA008748 / NCI NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS T32 CA009676 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS U24 CA144025 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS P30 ES013508 / NIEHS NIH HHS U24 CA210949 / NCI NIH HHS U24 CA143848 / NCI NIH HHS R01 CA163722 / NCI NIH HHS
- Language
- English
- Date published
- 04/05/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Internal Medicine
- Record Identifier
- 9984185172002771
Metrics
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