Transcriptomics

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A platform of patient-derived tumor xenografts (EOC-xenografts) to recapitulate the clinicopathology and genetic alterations of ovarian cancer


ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. On the basis of its histopathology and molecular-genomic changes ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC-xenografts that recapitulate the molecular and biological heterogeneity of human ovarian cancer. Thirty-four EOC-xenografts were successfully established, either subcutaneously or intraperitoneally, in nude mice. The xenografts were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. After orthotopic transplantation in the bursa of the mouse ovary, they disseminate into the organs of the peritoneal cavity and produce ascites, typical of ovarian cancer. Gene expression analysis and mutation status indicated a high degree of similarity with the original patient and discriminate different subsets of xenografts. They were very responsive, responsive and resistant to cisplatin, resembling the clinical situation in ovarian cancer. This panel of patient-derived EOC-xenografts that recapitulate the recently type I and type II classification serves to study the biology of ovarian cancer, identify tumor-specific molecular markers and develop novel treatment modalities. EOC-xenografts collected from subcutis, abdominal masses and ascitic fluid of mice engrafted with tumors at different passages (from 1 to 6) and from patient specimens, underwent one-color microarray-based gene expression profiling. To assess the amount of human- and mouse-derived cells in the xenograft tumors, total RNA was evaluated by species specific qPCR assays for beta actin. Only samples with a human RNA content > 75% were analyzed. Nine patient specimens and 62 xenograft samples (representing 29 EOC-xenograft models) underwent gene expression analysis with SurePrint G3 Human GE V2 8x60K microarrays.

ORGANISM(S): Homo sapiens  

SUBMITTER: Giovanna Damia   Francesca Bizzaro  Carmen Ghilardi  Paola Ostano  Marta Cesca  Monica Ganzinelli  Patrizia Perego  Francesca Ricci  Alessandro Buda  Raffaella Giavazzi  Robert Fruscio  Alessandra Decio  Maria R Bani  Federica Guffanti  Mauro Signorelli  giovanna chiorino  Giovanna Chiorino 

PROVIDER: E-GEOD-56920 | ArrayExpress | 2015-01-07

SECONDARY ACCESSION(S): GSE56920PRJNA244934

REPOSITORIES: GEO, ArrayExpress

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. On the basis of its histopathology and molecular-genomic changes, ovarian cancer has been divided into subtypes, each with distinct biology and outcome. The aim of this study was to develop a panel of patient-derived EOC xenografts that recapitulate the molecular and biologic heterogeneity of human ovarian cancer. Thirty-four EOC xenografts were successfully established, either subcutaneously or intraperitoneally, in nude  ...[more]

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