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

[1] Biobanking of patient and patient-derived xenograft ovarian tumour tissue: efficient preservation with low and high fetal calf serum based methods [J].

Alkema, Nicolette G. ;

Tomar, Tushar ;

Duiker, Evelien W. ;

Meersma, Gert Jan ;

Klip, Harry ;

van der Zee, Ate G. J. ;

Wisman, G. Bea A. ;

de Jong, Steven .

SCIENTIFIC REPORTS, 2015, 5

[2] Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors [J].

Ananda, Guruprasad ;

Mockus, Susan ;

Lundquist, Micaela ;

Spotlow, Vanessa ;

Simons, Al ;

Mitchell, Talia ;

Stafford, Grace ;

Philip, Vivek ;

Stearns, Timothy ;

Srivastava, Anuj ;

Barter, Mary ;

Rowe, Lucy ;

Malcolm, Joan ;

Bult, Carol ;

Karuturi, Radha Krishna Murthy ;

Rasmussen, Karen ;

Hinerfeld, Douglas .

EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2015, 98 (01) :106-112

[3]

[Anonymous], 2024, Easy Fisher Exact Test Calculator

[4] Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays [J].

Aryee, Martin J. ;

Jaffe, Andrew E. ;

Corrada-Bravo, Hector ;

Ladd-Acosta, Christine ;

Feinberg, Andrew P. ;

Hansen, Kasper D. ;

Irizarry, Rafael A. .

BIOINFORMATICS, 2014, 30 (10) :1363-1369

[5] QuPath: Open source software for digital pathology image analysis [J].

Bankhead, Peter ;

Loughrey, Maurice B. ;

Fernandez, Jose A. ;

Dombrowski, Yvonne ;

Mcart, Darragh G. ;

Dunne, Philip D. ;

McQuaid, Stephen ;

Gray, Ronan T. ;

Murray, Liam J. ;

Coleman, Helen G. ;

James, Jacqueline A. ;

Salto-Tellez, Manuel ;

Hamilton, Peter W. .

SCIENTIFIC REPORTS, 2017, 7

[6] Patient-derived xenografts undergo mouse-specific tumor evolution [J].

Ben-David, Uri ;

Ha, Gavin ;

Tseng, Yuen-Yi ;

Greenwald, Noah F. ;

Oh, Coyin ;

Shih, Juliann ;

McFarland, James M. ;

Wong, Bang ;

Boehm, Jesse S. ;

Beroukhim, Rameen ;

Golub, Todd R. .

NATURE GENETICS, 2017, 49 (11) :1567-+

[7] ARID1A mutation sensitizes most ovarian clear cell carcinomas to BET inhibitors [J].

Berns, Katrien ;

Caumanns, Joseph J. ;

Hijmans, E. Marielle ;

Gennissen, Annemiek M. C. ;

Severson, Tesa M. ;

Evers, Bastiaan ;

Wisman, G. Bea A. ;

Meersma, Gert Jan ;

Lieftink, Cor ;

Beijersbergen, Roderick L. ;

Itamochi, Hiroaki ;

van der Zee, Ate G. J. ;

de Jong, Steven ;

Bernards, Rene .

ONCOGENE, 2018, 37 (33) :4611-4625

[8]

bioconductor, A cross-package Bioconductor workflow for analysing methylation array data

[9] Prevention of Human Lymphoproliferative Tumor Formation in Ovarian Cancer Patient-Derived Xenografts [J].

Butler, Kristina A. ;

Hou, Xiaonan ;

Becker, Marc A. ;

Zanfagnin, Valentina ;

Enderica-Gonzalez, Sergio ;

Visscher, Daniel ;

Kalli, Kimberly R. ;

Tienchaianada, Piyawan ;

Haluska, Paul ;

Weroha, S. John .

NEOPLASIA, 2017, 19 (08) :628-636

[10] Low-dose triple drug combination targeting the PI3K/AKT/mTOR pathway and the MAPK pathway is an effective approach in ovarian clear cell carcinoma [J].

Caumanns, Joseph J. ;

van Wijngaarden, Anne ;

Kol, Arjan ;

Meersma, Gert J. ;

Jalving, Mathilde ;

Bernards, Rene ;

van der Zee, Ate G. J. ;

Wisman, G. Bea A. ;

de Jong, Steven .

CANCER LETTERS, 2019, 461 :102-111

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