Journal article
Comprehensive Characterization of Cancer Driver Genes and Mutations
Cell, Vol.173(2), pp.371-1035
04/05/2018
DOI: 10.1016/j.cell.2018.02.060
PMCID: PMC6029450
PMID: 29625053
Abstract
Identifying molecular cancer drivers is critical for precision oncology. Multiple advanced algorithms to identify drivers now exist, but systematic attempts to combine and optimize them on large datasets are few. We report a PanCancer and PanSoftware analysis spanning 9,423 tumor exomes (comprising all 33 of The Cancer Genome Atlas projects) and using 26 computational tools to catalog driver genes and mutations. We identify 299 driver genes with implications regarding their anatomical sites and cancer/cell types. Sequence-and structure-based analyses identified > 3,400 putative missense driver mutations supported by multiple lines of evidence. Experimental validation confirmed 60%-85% of predicted mutations as likely drivers. We found that > 300 MSI tumors are associated with high PD-1/PD-L1, and 57% of tumors analyzed harbor putative clinically actionable events. Our study represents the most comprehensive discovery of cancer genes and mutations to date and will serve as a blueprint for future biological and clinical endeavors.
Details
- Title: Subtitle
- Comprehensive Characterization of Cancer Driver Genes and Mutations
- Creators
- Matthew H. Bailey - Washington University in St. LouisCollin Tokheim - Johns Hopkins UniversityEduard Porta-Pardo - Barcelona Supercomputing CenterSohini Sengupta - Washington University in St. LouisDenis Bertrand - Genome Institute of SingaporeAmila Weerasinghe - Washington University in St. LouisMichael C. Wendl - Washington University in St. LouisJaegil Kim - Broad InstituteBrendan Reardon - Dana-Farber Cancer InstitutePatrick Kwok-Shing Ng - Univ Texas MD Anderson Canc Ctr, Sheikh Khalifa Bin Zayed Al Nahyan Inst Personali, Houston, TX 77030 USAKang Jin Jeong - The University of Texas MD Anderson Cancer CenterSong Cao - Washington University in St. LouisZixing Wang - The University of Texas MD Anderson Cancer CenterJianjiong Gao - Memorial Sloan Kettering Cancer CenterQingsong Gao - Washington University in St. LouisFang Wang - The University of Texas MD Anderson Cancer CenterEric Minwei Liu - Weill Cornell MedicineLoris Mularoni - Institute for Research in BiomedicineCarlota Rubio-Perez - Institute for Research in BiomedicineNiranjan Nagarajan - Genome Institute of SingaporeIsidro Cortes-Ciriano - University of CambridgeDaniel Cui Zhou - Washington University in St. LouisWen-Wei Liang - Washington University in St. LouisJulian M. Hess - Broad InstituteVenkata D. Yellapantula - Washington University in St. LouisDavid Tamborero - Institute for Research in BiomedicineAbel Gonzalez-Perez - Institute for Research in BiomedicineChayaporn Suphavilai - Genome Institute of SingaporeJia Yu Ko - Genome Institute of SingaporeEkta Khurana - Cornell UniversityPeter J. Park - Harvard UniversityEliezer M. Van Allen - Dana-Farber Cancer InstituteHan Liang - The University of Texas MD Anderson Cancer CenterMichael S. Lawrence - Massachusetts General HospitalAdam Godzik - Sanford Burnham Prebys Medical Discovery InstituteNuria Lopez-Bigas - Institute for Research in BiomedicineJosh Stuart - Univ Calif Santa Cruz, 1156 High St, Santa Cruz, CA 95064 USADavid Wheeler - Baylor College of MedicineGad Getz - Broad InstituteKen Chen - The University of Texas MD Anderson Cancer CenterAlexander J. Lazar - The University of Texas MD Anderson Cancer CenterGordon B. Mills - The University of Texas MD Anderson Cancer CenterRachel Karchin - Johns Hopkins UniversityLi Ding - Washington University in St. LouisCancer Genome Atlas Research Network
- Contributors
- M M Milhem (Contributor) - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.173(2), pp.371-1035
- Publisher
- Elsevier
- DOI
- 10.1016/j.cell.2018.02.060
- PMID
- 29625053
- PMCID
- PMC6029450
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Number of pages
- 33
- Grant note
- U24 CA143799; U24 CA143835; U24 CA143840; U24 CA143843; U24 CA143845; U24 CA143848; U24 CA143858; U24 CA143866; U24 CA143867; U24 CA143882; U24 CA143883; U24 CA144025; P30 CA016672; BP 2016-00296; U24 CA211006 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R25DA027995 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission U54 HG003273; U54 HG003067; U54 HG003079 / NIH grants from the NHGRI R01HG009711 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) F32GM072403 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) P30CA016672 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 04/05/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359579102771
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