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

被引：1

作者：

Caumanns, Joseph J. ^{[1
]}

Li, Shang ^{[2
]}

Meersma, Gert J. ^{[2
]}

Duiker, Evelien W. ^{[3
]}

van der Zee, Ate G. J. ^{[1
]}

Wisman, G. Bea A. ^{[1
]}

de Jong, Steven ^{[2
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Canc Res Ctr Groningen, Dept Gynecol Oncol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Canc Res Ctr Groningen, Dept Med Oncol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands

[3] Univ Groningen, Univ Med Ctr Groningen, Canc Res Ctr Groningen, Dept Pathol & Med Biol, Hanzeplein 1, NL-9713 GZ Groningen, Netherlands

来源：

SCIENTIFIC REPORTS | 2025年 / 15卷 / 01期

关键词：

Ovarian clear cell carcinoma; Patient derived xenografts; ARID1A; Copy number alterations; DNA methylation; CANCER; TUMOR; MUTATIONS; MODELS; ARID1A;

D O I：

10.1038/s41598-025-86384-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (triangle beta-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.

引用

页数：15

共 54 条

[41] Cytoscape: A software environment for integrated models of biomolecular interaction networks [J].

Shannon, P ;

Markiel, A ;

Ozier, O ;

Baliga, NS ;

Wang, JT ;

Ramage, D ;

Amin, N ;

Schwikowski, B ;

Ideker, T .

GENOME RESEARCH, 2003, 13 (11) :2498-2504

[42] The OncoLifeS data-biobank for oncology: a comprehensive repository of clinical data, biological samples, and the patient's perspective [J].

Sidorenkov, Grigory ;

Nagel, Janny ;

Meijer, Coby ;

Duker, Jacko J. ;

Groen, Harry J. M. ;

Halmos, Gyorgy B. ;

Oonk, Maaike H. M. ;

Oostergo, Rene J. ;

van der Vegt, Bert ;

Witjes, Max J. H. ;

Nijland, Marcel ;

Havenga, Klaas ;

Maduro, John H. ;

Gietema, Jourik A. ;

de Bock, Gertruida H. .

JOURNAL OF TRANSLATIONAL MEDICINE, 2019, 17 (01)

[43] Identification of Novel Therapeutic Targets in Microdissected Clear Cell Ovarian Cancers [J].

Stany, Michael P. ;

Vathipadiekal, Vinod ;

Ozbun, Laurent ;

Stone, Rebecca L. ;

Mok, Samuel C. ;

Xue, Hui ;

Kagami, Takashi ;

Wang, Yuwei ;

McAlpine, Jessica N. ;

Bowtell, David ;

Gout, Peter W. ;

Miller, Dianne M. ;

Gilks, C. Blake ;

Huntsman, David G. ;

Ellard, Susan L. ;

Wang, Yu-Zhuo ;

Vivas-Mejia, Pablo ;

Lopez-Berestein, Gabriel ;

Sood, Anil K. ;

Birrer, Michael J. .

PLOS ONE, 2011, 6 (07)

[44] Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles [J].

Subramanian, A ;

Tamayo, P ;

Mootha, VK ;

Mukherjee, S ;

Ebert, BL ;

Gillette, MA ;

Paulovich, A ;

Pomeroy, SL ;

Golub, TR ;

Lander, ES ;

Mesirov, JP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (43) :15545-15550

[45] Genomic Analysis Reveals the Molecular Heterogeneity of Ovarian Clear Cell Carcinomas [J].

Tan, David S. P. ;

Iravani, Marjan ;

McCluggage, W. Glenn ;

Lambros, Maryou B. K. ;

Milanezi, Fernanda ;

Mackay, Alan ;

Gourley, Charles ;

Geyer, Felipe C. ;

Vatcheva, Radost ;

Millar, Joanne ;

Thomas, Karen ;

Natrajan, Rachael ;

Savage, Kay ;

Fenwick, Kerry ;

Williams, Alistair ;

Jameson, Charles ;

El-Bahrawy, Mona ;

Gore, Martin E. ;

Gabra, Hani ;

Kaye, Stanley B. ;

Ashworth, Alan ;

Reis-Filho, Jorge S. .

CLINICAL CANCER RESEARCH, 2011, 17 (06) :1521-1534

[46] Comparative analysis of response to treatments and molecular features of tumor-derived organoids versus cell lines and PDX derived from the same ovarian clear cell carcinoma [J].

Thorel, Lucie ;

Morice, Pierre-Marie ;

Paysant, Hippolyte ;

Florent, Romane ;

Babin, Guillaume ;

Thomine, Cecilia ;

Perreard, Marion ;

Abeilard, Edwige ;

Giffard, Florence ;

Brotin, Emilie ;

Denoyelle, Christophe ;

Villenet, Celine ;

Sebda, Sheherazade ;

Briand, Melanie ;

Joly, Florence ;

Dolivet, Enora ;

Goux, Didier ;

Blanc-Fournier, Cecile ;

Jeanne, Corinne ;

Villedieu, Marie ;

Meryet-Figuiere, Matthieu ;

Figeac, Martin ;

Poulain, Laurent ;

Weiswald, Louis-Bastien .

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2023, 42 (01)

[47] Genome-wide methylation profiling of ovarian cancer patient-derived xenografts treated with the demethylating agent decitabine identifies novel epigenetically regulated genes and pathways [J].

Tomar, Tushar ;

de Jong, Steven ;

Alkema, Nicolette G. ;

Hoekman, Rieks L. ;

Meersma, Gert Jan ;

Klip, Harry G. ;

van der Zee, Ate G. J. ;

Wisman, G. Bea A. .

GENOME MEDICINE, 2016, 8

[48] Molecular correlates of platinum response in human high-grade serous ovarian cancer patient-derived xenografts [J].

Topp, Monique D. ;

Hartley, Lynne ;

Cook, Michele ;

Heong, Valerie ;

Boehm, Emma ;

McShane, Lauren ;

Pyman, Jan ;

McNally, Orla ;

Ananda, Sumitra ;

Harrell, Marisol ;

Etemadmoghadam, Dariush ;

Galletta, Laura ;

Alsop, Kathryn ;

Mitchell, Gillian ;

Fox, Stephen B. ;

Kerr, Jeffrey B. ;

Hutt, Karla J. ;

Kaufmann, Scott H. ;

Swisher, Elizabeth M. ;

Bowtell, David D. ;

Wakefield, Matthew J. ;

Scott, Clare L. .

MOLECULAR ONCOLOGY, 2014, 8 (03) :656-668

[49] Tumorgrafts as In Vivo Surrogates for Women with Ovarian Cancer [J].

Weroha, S. John ;

Becker, Marc A. ;

Enderica-Gonzalez, Sergio ;

Harrington, Sean C. ;

Oberg, Ann L. ;

Maurer, Matthew J. ;

Perkins, Sarah E. ;

AlHilli, Mariam ;

Butler, Kristina A. ;

McKinstry, Sarah ;

Fink, Stephanie ;

Jenkins, Robert B. ;

Hou, Xiaonan ;

Kalli, Kimberly R. ;

Goodman, Karin M. ;

Sarkaria, Jann N. ;

Karlan, Beth Y. ;

Kumar, Amanika ;

Kaufmann, Scott H. ;

Hartmann, Lynn C. ;

Haluska, Paul .

CLINICAL CANCER RESEARCH, 2014, 20 (05) :1288-1297

[50]

Wickham H., 2016, Ggplot2: elegant graphics for data analysis, DOI [10.1007/978-3-319-24277-4, DOI 10.1007/978-3-319-24277-4]

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