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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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Added by mollevi
Group name EquipeMY
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 Pierre-Emmanuel Colombo
Author Stanislas du Manoir
Author Béatrice Orsett
Author Rui Bras-Gonçalves
Author Mario B. Lambros
Author Alan MacKay
Author Tien-Tuan Nguyen
Author Florence Boissière
Author Didier Pourquier
Author Frédéric Bibeau
Author Jorge S. Reis-Filho
Author Charles 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
Issue 29
Pages 28327-28340
Date Sep 29, 2015
Journal Abbr Oncotarget
Language eng
DOI 10.18632/oncotarget.5069
ISSN 1949-2553
Library Catalog PubMed
Extra PMID: 26334103 PMCID: PMC4695063
Tags Adult, Aged, Aged, 80 and over, Animals, Clone Cells, CNC, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Heterografts, Humans, Mice, Nude, Middle Aged, mutations, Neoplasm Metastasis, Neoplasm Recurrence, Local, oligoclonality, original, Ovarian Neoplasms, PDX, Prognosis, Survival Analysis, Transplantation, Heterologous
Date Added 2018/11/13 - 17:26:10
Date Modified 2019/05/21 - 14:52:11


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