Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure

Oncotarget
Pierre-Emmanuel ColomboCharles 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 xe...Continue Reading

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Jan 24, 2019·Cellular and Molecular Life Sciences : CMLS·Aalia BatoolYi-Xun Liu
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Feb 23, 2020·Cells·Concetta D'AmbrosioMartina Olivero
Mar 20, 2021·Molecular Therapy Oncolytics·Qian ZhangXiaoli Tian

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Methods Mentioned

BETA
xenografts
exome sequencing
surgical resection
dissection
electrophoresis
Assay
Fluorescence
PCR

Software Mentioned

ensembl
IGV
Mutation Surveyor
Nexus
Variant Effect Predictor
Galaxy
GATK
GenomeStudio
R
Illumina GenomeStudio

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