Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure.
Advanced Epithelial Ovarian Cancer (EOC) patients frequently relapse by 24 months and develop resistant disease. Research on EOC therapies relies on cancer cell lines established decades ago making Patient Derived Xenografts (PDX) attractive models, because they are faithful representations of the original tumor. We established 35 ovarian cancer PDXs resulting from the original graft of 77 EOC samples onto immuno-compromised mice. PDXs covered the diversity of EOC histotypes and graft take was correlated with early patient death. Fourteen PDXs were characterized at the genetic and histological levels. PDXs reproduced phenotypic features of the ovarian tumors of origin and conserved the principal characteristics of the original copy number change (CNC) profiles over several passages. However, CNC fluctuations in specific subregions comparing the original tumor and the PDXs indicated the oligoclonal nature of the original tumors. Detailed analysis by CGH, FISH and exome sequencing of one case, for which several tumor nodules were sampled and grafted, revealed that PDXs globally maintained an oligoclonal structure. No overgrowth of a particular subclone present in the original tumor was observed in the PDXs. This suggested that xenotransplantation of ovarian tumors and growth as PDX preserved at least in part the clonal diversity of the original tumor. We believe our data reinforce the potential of PDX as exquisite tools in pre-clinical assays.
['Colombo|Pierre-Emmanuel|PE|', 'du Manoir|Stanislas|S|', 'Orsett|Béatrice|B|', 'Bras-Gonçalves|Rui|R|', 'Lambros|Mario B|MB|', 'MacKay|Alan|A|', 'Nguyen|Tien-Tuan|TT|', 'Boissière|Florence|F|', 'Pourquier|Didier|D|', 'Bibeau|Frédéric|F|', 'Reis-Filho|Jorge S|JS|', 'Theillet|Charles|C|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000818:Animals D002999:Clone Cells D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D064593:Heterografts D006801:Humans D008819:Mice, Nude D008875:Middle Aged D009362:Neoplasm Metastasis D009364:Neoplasm Recurrence, Local D010051:Ovarian Neoplasms D011379:Prognosis D016019:Survival Analysis D014183:Transplantation, Heterologous
oligoclonality ovarian cancer PDX CNC mutations