title: Expression profiling of primary and metastatic ovarian tumors reveals differences indicative of aggressive disease.
abstract: The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America; Center for Genomics and Proteomics, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Brodsky
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Souriya
authors.initials: S
authors.lastname: Vang
authors.affiliation: Program in Women's Oncology, Department of Obstetrics and Gynecology, Women and Infants' Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Shannon
authors.initials: S
authors.lastname: MacLaughlan
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island, United States of America; Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America; Department of Computer Science, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Hsin-Ta
authors.initials: HT
authors.lastname: Wu
authors.affiliation: Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Jovian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, Women and Infants' Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, United States of America.
authors.forename: Margaret
authors.initials: M
authors.lastname: Steinhoff
authors.affiliation: Vancouver Prostate Centre, Vancouver, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: Collins
authors.affiliation: Institute for Life Sciences, University of Southampton, Southampton, England.
authors.forename: Peter J S
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: Center for Computational Molecular Biology, Brown University, Providence, Rhode Island, United States of America; Department of Computer Science, Brown University, Providence, Rhode Island, United States of America.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Raphael
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America.
authors.forename: Laurent
authors.initials: L
authors.lastname: Brard
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D016000:Cluster Analysis; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D009362:Neoplasm Metastasis; D009852:Omentum / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
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