Integrated genomic analyses of ovarian carcinoma
Debra BellDivision of Anatomic Pathology, Mayo Clinic, Rochester, 55905, Minnesota, USAAndrew BerchuckDivision of Gynecologic Oncology/Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, 27708, North Carolina, USAMichael J. BirrerMassachusetts General HospitalMarcin ImielińskiGynecologic Oncology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USAJeremy ChienDivision of Experimental Pathology, Mayo Clinic, Rochester, 55905, Minnesota, USAD. W. CramerDepartment of Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital, Boston, 02115, Massachusetts, USANarciso OlveraDepartment of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAFanny DaoDepartment of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAD. A. LevineDepartment of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAD. A. LevineDepartment of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USARajiv DhirDepartment of Pathology, University of Pittsburgh, Pittsburgh, 15213, Pennsylvania, USAPhilip J. DiSaiaGynecologic Oncology Group, University of California Irvine, Irvine, 92697, California, USAHani GabraDepartment of Surgery and Cancer, Ovarian Cancer Action Research Centre, Imperial College London Hammersmith Campus, London W12 0NN, UKKaren Smith‐McCuneDepartment of Obstetrics, Gynecology and Reproductive Services, University of California San Francisco, San Francisco, 94143, California, USAPat GlennDepartment of Obstetrics, Gynecology and Reproductive Services, University of California San Francisco, San Francisco, 94143, California, USAA. K. GodwinDepartment of Medical Oncology, Women’s Cancer Program, Fox Chase Cancer Center, Philadelphia, 19111, Pennsylvania, USASandra OršulićCedars-Sinai Medical Center, Los Angeles, United StatesBeth Y. KarlanDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Geffen School of Medicine at UCLA, Los Angeles, 90048, California, USAJenny GrossWomen’s Cancer Research Institute at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Geffen School of Medicine at UCLA, Los Angeles, 90048, California, USAL HartmannDivision of Medical Oncology, Mayo Clinic, Rochester, 55905, Minnesota, USAMei HuangDepartment of Pathology, Fox Chase Cancer Center, Philadelphia, 19111, Pennsylvania, USADavid G. HuntsmanCenter for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1G1, CanadaSteve E. KallogerCenter for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1G1, CanadaBrenda RabenoDepartment of Pathology, Christiana Care Health Services, Newark, 19718, Delaware, USAMary IacoccaDepartment of Pathology, Christiana Care Health Services, Newark, 19718, Delaware, USABeth Y. KarlanDepartment of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Geffen School of Medicine at UCLA, Los Angeles, 90048, California, USAG.B. MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USAG. B. MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USAJ. N. WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USAG.B. MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USAG. B. MillsDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USAC. MorrisonDivision of Molecular Pathology, Roswell Park Cancer Institute, Buffalo, 14263, New York, USAC. MorrisonDivision of Molecular Pathology, Roswell Park Cancer Institute, Buffalo, 14263, New York, USAD. MutchDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, Washington University School of Medicine in St Louis, St Louis, 63110, Missouri, USAKay J. ParkDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USANicholas J. PetrelliDepartment of Surgery, Helen F Graham Cancer Center at Christina Care, Newark, 19713, Delaware, USAJanet S. RaderDepartment of Obstetrics and Gynecology, Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, 53226, Wisconsin, USABranimir I. ŠikićDivision of Oncology, Department of Medicine, Stanford University School of Medicine, Palo Alto, 94304, California, USAAnil K. SoodCenter for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, 77230, Texas, USADavid D.L. BowtellResearch Division, Peter MacCallum Cancer Centre, Locked Bag 1, A’Beckett St, Melbourne, 8006, Victoria, AustraliaScott MorrisInternational Genomics Consortium, Phoenix, 85004, Arizona, USAPeggy YenaInternational Genomics Consortium, Phoenix, 85004, Arizona, USAMichael J HatfieldInternational Genomics Consortium, Phoenix, 85004, Arizona, USAJoseph PaulauskisHarvard University, Cambridge, United StatesTroy SheltonInternational Genomics Consortium, Phoenix, 85004, Arizona, USARobert PennyInternational Genomics Consortium, Phoenix, 85004, Arizona, USAPaul RhodesInternational Genomics Consortium, Phoenix, 85004, Arizona, USARobert PennyInternational Genomics Consortium, Phoenix, 85004, Arizona, USAMark E. ShermanInternational Genomics Consortium, Phoenix, 85004, Arizona, USADonata GrimmInternational Genomics Consortium, Phoenix, 85004, Arizona, USASherri Z. MillisInternational Genomics Consortium, Phoenix, 85004, Arizona, USAJoseph R. TestaCancer Biology Program, Fox Chase Cancer Center, Philadelphia, 19111, Pennsylvania, USADavid A. WheelerHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USALora LewisHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAY.-Q. WuHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAJennifer DrummondHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAIrene NewshamHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAM. B. MorganHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAJireh SantibanezHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAC. KovarHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAHuyen DinhHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAKuo-Ching ChangHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USALisa R. TreviñoHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAC. J. CreightonHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USARichard A. GibbsHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAPreethi H. GunaratneHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAGerald FowlerHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAM. WangHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAAlicia HawesHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USADonna M. MuznyHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAJ. G. ReidHuman Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USAG. GetzCancer Genome & Medical Resequencing Projects, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAMatthew MeyersonCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USAAndrey SivachenkoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAC. H. MermelDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USAAlex H. RamosCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USAAndrey SivachenkoThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAK. CibulskisMedical Sequencing Analysis and Informatics, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAR. W. ParkThe Center for Biomedical Informatics, Harvard Medical School, Boston, 02115, Massachusetts, USAS. L. CarterDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USARobert C. OnofrioThe 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, USAEric S. LanderDepartment of Biology, Massachusetts Institute of Technology, Cambridge, 02142, Massachusetts, USAL. 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, USAKristin ArdlieThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAGaddy GetzCancer Genome & Medical Resequencing Projects, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAHuy NguyenThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAR. G. W. VerhaakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USAMichael S. LawrenceThe 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, USASumeet GuptaThe 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, USAMike NobleThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USADiana HubbardCenter for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USAK. CibulskisMedical Sequencing Analysis and Informatics, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USAKristian CibulskisMedical Sequencing Analysis and Informatics, The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, 02142, Massachusetts, USA
2011en
ABI
Аннотация
A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology. The Cancer Genome Atlas (TCGA) project reports here its analysis of messenger RNA and microRNA expression, promoter methylation, DNA copy number and exome sequences in 489 high-grade serous ovarian adenocarcinomas. The analyses help establish new tumour subtypes. Among other insights is the finding that while the gene encoding p53 tumour suppressor is mutated in almost all tumours, nine other loci including NF1, BRCA1, BRCA2, RB1 and CDK12 carry recurrent albeit low-prevalence mutations. Homologous recombination is defective in about half of the tumours studied, and Notch and FOXM1 signalling are involved in the pathophysiology.
Перевод пока недоступен
Идентификаторы
Цитирования и источники
Цитирований: 2Использованных источников: 0