Comprehensive genomic characterization of squamous cell lung cancers
Gad GetzGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAStephen E. SchumacherEli and Edythe Broad FoundationPetar StojanovThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USASachet ShuklaDepartment of Medical Oncology, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.,Hailei ZhangDepartment of Medical Oncology, Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.,Kristian CibulskisThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USANam H. PhoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAMatthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Eric S. LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USAHelga ThorvaldsdottirThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USABarbara TabakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Nils GehlenborgThe Center for Biomedical Informatics, Harvard Medical School, Boston, 02115, Massachusetts, USAAndrey SivachenkoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAMarc-Danie NazaireThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAPei LinThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAMichael NobleThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USALihua ZouThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAJim RobinsonThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USADoug VoetThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USARameen BeroukhimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Jill MesirovThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USADouglas VoetThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAMarcin ImielinskiDepartment of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USAPeter S. HammermanEli and Edythe Broad FoundationPeter S. HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Huy NguyenThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAWendy WincklerGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAAaron McKennaThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USALynda ChinDepartment of Dermatology, Harvard Medical School, Boston, 02115, Massachusetts, USAAndrew CrenshawThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAJuok ChoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAElena HelmanThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USASpring Yingchun LiuThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAScott L. CarterThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAGordon SaksenaThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAMichael S. LawrenceEli and Edythe Broad FoundationDaniel DiCaraThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USARui JingThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USABryan HernandezThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAAndrew D. CherniackThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAAndrey SivachenkoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, 02142, Massachusetts, USAStephen E. SchumacherDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Rameen BeroukhimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Barbara TabakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Bruce E. JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Chang-Jiun WuDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.,Peter S. HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,David KwiatkowskiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Bruce JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Peter S. HammermanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Matthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Lynda ChinDepartment of Dermatology, Harvard Medical School, Boston, 02115, Massachusetts, USAEric S. LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USAEric S. LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USACarrie SougnezDepartment of Systems Biology, Harvard University, Boston, Massachusetts 02115, USA.,Gad GetzGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USACarrie SougnezDepartment of Systems Biology, Harvard University, Boston, Massachusetts 02115, USA.,Stacey GabrielGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAKristin ArdlieGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USARobert C. OnofrioGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAGad GetzGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAWendy WincklerGenetic Analysis Platform, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAMarcin ImielinskiDepartment of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USAMatthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.,Marcin ImielinskiDepartment of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USAYongjun ZhaoCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Andrew J. MungallCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Angela TamCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Karen MungallCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Andy ChuCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,An HeCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Miruna BalasundaramCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Elizabeth ChunCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Richard VarholCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Robert A. HoltCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Jacqueline E. ScheinCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,A. Gordon RobertsonCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Andy ChuCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Carrie HirstCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Marco A. MarraCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Martin HirstCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Eric ChuahCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Robin J. N. CoopeCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Hye-Jung E. ChunCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Dominik StollCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Yaron S. N. ButterfieldCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Ka Ming NipCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Haiyan I. LiCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Erin PleasanceCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Jared R. SlobodanCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Ranabir GuinCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Nina ThiessenCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Gordon RobertsonCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Andy MungallCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Darlene LeeCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Thomas ZengCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Michael MayoCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Andy ChuCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Richard CorbettCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,Richard A. MooreCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z, Canada.,
2012en
ABI
Аннотация
Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers. Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied. The Cancer Genome Atlas consortium has analysed 178 lung squamous cell carcinomas, a common type of lung cancer for which comprehensive genomic analyses have not previously been available. The researchers report that this tumour type is characterized by complex genomic alterations, with recurrent mutations in 18 genes, including TP53 in nearly all samples. They also report frequent mutations in squamous differentiation genes. Collectively, these analyses identify potential therapeutic targets worthy of further investigation.
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