Establishment and characterization of ovarian clear cell carcinoma patient-derived xenografts

Bibliographic Details
Title: Establishment and characterization of ovarian clear cell carcinoma patient-derived xenografts
Authors: Joseph J. Caumanns, Shang Li, Gert J. Meersma, Evelien W. Duiker, Ate G. J. van der Zee, G. Bea A. Wisman, Steven de Jong
Source: Scientific Reports, Vol 15, Iss 1, Pp 1-15 (2025)
Publisher Information: Nature Portfolio, 2025.
Publication Year: 2025
Collection: LCC:Medicine
LCC:Science
Subject Terms: Ovarian clear cell carcinoma, Patient derived xenografts, ARID1A, Copy number alterations, DNA methylation, Medicine, Science
More Details: Abstract Interest in understanding the high chemoresistance and poor prognosis of advanced ovarian clear cell carcinoma (OCCC) is rising. Patient-derived xenografts (PDX) are widely used in vivo models because of their supposedly accurate morphologic and (epi)genetic representation of patient tumors. Here, we established five subcutaneous OCCC PDXs. The PDX.F1 engraftment success rate was over 30% with similar latency time and growth speed of PDX.F2. ARID1A, PTEN, ATM, BRCA1 and PIK3CA mutations were found in matched tumors and PDXs. ARID1A protein loss was further verified by immunohistochemical staining. Cyclophilin A staining depicted the replacement of human stroma by mouse stroma in PDX.F2, while PAS/PAS-D staining confirmed cellular glycogen accumulation in OCCC tumors and PDXs. SNP array and Infinium MethylationEPIC BeadChip array data analysis demonstrated the copy number alterations and DNA methylation signatures of genome-wide and tumor-driver genes in PDXs generally resembled their patients’ tumors. Promoter CpG islands of a small number of genes, enriched in PRC2/histone methylation related gene-sets, gained methylation (△β-value > 0.4) in PDXs vs patient tumors. In conclusion, the high phenotypic and molecular similarity allows the established PDXs to serve as potential preclinical models for future translational research of OCCC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-025-86384-2
Access URL: https://doaj.org/article/d5737f9e04b54f13ba24d310ffcda2ed
Accession Number: edsdoj.5737f9e04b54f13ba24d310ffcda2ed
Database: Directory of Open Access Journals
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More Details
ISSN:20452322
DOI:10.1038/s41598-025-86384-2
Published in:Scientific Reports
Language:English