Brenda Rabeno

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.

Click to increase image sizeClick to decrease image size Additional informationNotes on contributorsRobert A. SikesRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Randall L. DuncanRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Kelvin LeeRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Kirk CzymmekRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Karl SteinerRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Ayyappan K. RajasekaranRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Mary IacoccaRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Brenda RabenoRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Zohra Ali Khan CattsRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Abraham JosephRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Bruce BomanRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.Nicholas PetrelliRobert A. Sikes, PhD, is director of the Center for Translational Cancer Research, associate professor Department of Biological Sciences, University of Delaware, Newark, Del.; Randall L. Duncan, PhD, is professor and chair of the Department of Biological Sciences, University of Delaware, Newark, Del.; Kelvin Lee, PhD, is the Gore Professor of Engineering, University of Delaware, and director of the Delaware Biotechnology Institute, Newark, Del.;Kirk Czymmek, PhD, is associate professor, Department of Biological Sciences, director Delaware Biotechnology Institute Bio-Imaging Center, director Center for Translational Cancer Research Core Facility, Newark, Del.; Karl Steiner, PhD, is senior associate provost for Research Development, professor Electrical and Computer Engineering, University of Delaware, Newark, Del.; Ayyappan K. Rajasekaran, PhD, is director Nemours Center for Childhood Cancer Research, Alfred I. DuPont Hospital for Children, Newark, Del., affiliated scientist Department of Biological Sciences, University of Delaware, adjunct associate professor, Department of Material Science, University of Delaware, Newark, Del.; Mary Iacocca, MD, is director of the Tissue Procurement Facility, Helen F. Graham Cancer Center, Department of Pathology, Christiana Care, Newark, Del.; Brenda Rabeno, MBA, MT, is Biorepository Manager, Tissue Procurement Facility, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Zohra Ali Khan Catts, CGC, MS, is director of Genetic Counseling, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; Abraham Joseph, MA, MBA, CG, MB, DLM, is manager, Molecular Diagnostics, Center for Translational Cancer Research, Christiana Care, Newark, Del.; Bruce Boman, MD, PhD, is director of Cancer Genetics and Stem Cell Biology, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.; and Nicholas Petrelli is Bank of America Endowed Medical Director, Helen F. Graham Cancer Center, Christiana Care, Newark, Del.

SummaryThe Cancer Genome Atlas (TCGA) project has analyzed mRNA expression, miRNA expression, promoter methylation, and DNA copy number in 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa) and the DNA sequences of exons from coding genes in 316 of these tumors. These results show that HGS-OvCa is characterized by TP53 mutations in almost all tumors (96%); low prevalence but statistically recurrent somatic mutations in 9 additional 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 miRNA subtypes, four promoter methylation subtypes, a transcriptional signature associated with survival duration and shed new light on the impact on survival of tumors with BRCA1/2 and CCNE1 aberrations. Pathway analyses suggested that homologous recombination is defective in about half of tumors, and that Notch and FOXM1 signaling are involved in serous ovarian cancer pathophysiology.

e12035 Background: In September 2008, the Helen F. Graham Cancer Center and Christiana Care Health System received an award from the National Cancer Institute (NCI) to collect glioblastoma multiforme (GBM), squamous cell carcinoma of the lung, and ovarian serous cystadenocarcinoma tumor tissue along with corresponding normal specimens for TCGA. By January 2009 all of the required documentation including standard operating procedures, consent, and material transfer agreement had been submitted and IRB approval was obtained. In February 2009 tissue collection commenced. Methods: Implementation required addition of personnel, as well as buy-in from participating departments and individuals, and a continuing education plan. The addition of five full-time positions was deemed necessary. Three research nurses to screen, consent, and follow patients and two tissue procurement technicians to procure the surgical specimens from the operating room and process the tissue selected by a pathologist per the TCGA protocol were hired. Prior to collecting tissue, inservice sessions were held for surgeons, operating room staff, histology staff, and pathologists. Results: Shortly after collection began, the NCI gave approval for the collection of other tumor types in anticipation of an expansion list of tumor types, which was released in October 2009. The Table below lists the different tumor types that have successfully been collected and passed the stringent quality control requirements. Conclusions: In order to collect high-quality biospecimens in a community hospital setting it is essential to have dedicated staff for both screening, consenting, and following patients and for tissue handling. It is also necessary to educate and then maintain buy-in from the individuals and departments whose cooperation is required throughout the process. Tumor type # Eligible Glioblastoma multiforme 7 Serous cystadenocarcinoma 15 Squamous cell carcinoma 7 Lung adenocarcinoma 18 Colorectal adenocarcinoma 30 Infiltrating ductal carcinoma 5 Endometrial carcinoma 1 Total 83 No significant financial relationships to disclose.