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Epitranscriptomics & Cancer Adaptation : A.David

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Our research work focuses on the contribution of post-transcriptional mechanisms on cancer cell adaptation, in particular RNA epigenetic & translational control.

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Last modified by ircm doc
Group name EquipeCTCS
Item Type Journal Article
Title Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure
Creator Colombo et al.
Author P. E. Colombo
Author S. du Manoir
Author B. Orsett
Author R. Bras-Goncalves
Author M. B. Lambros
Author A. MacKay
Author T. T. Nguyen
Author F. Boissiere
Author D. Pourquier
Author F. Bibeau
Author J. S. Reis-Filho
Author C. Theillet
Abstract 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.
Publication Oncotarget
Volume 6
Pages 28327-40
Date Sep 29 2015
Journal Abbr Oncotarget
DOI 10.18632/oncotarget.5069
ISSN 1949-2553 (Electronic) 1949-2553 (Linking)
Tags original
Date Added 2018/11/14 - 15:25:02
Date Modified 2025/01/16 - 11:24:37
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