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
收藏
页数:15
相关论文
共 54 条
[11]   ARID1A mutant ovarian clear cell carcinoma: A clear target for synthetic lethal strategies [J].
Caumanns, Joseph J. ;
Wisman, G. Bea A. ;
Berns, Katrien ;
van der Zee, Ate G. J. ;
de Jong, Steven .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2018, 1870 (02) :176-184
[12]   Integrative Kinome Profiling Identifies mTORC1/2 Inhibition as Treatment Strategy in Ovarian Clear Cell Carcinoma [J].
Caumanns, Joseph J. ;
Berns, Katrien ;
Wisman, G. Bea A. ;
Fehrmann, Rudolf S. N. ;
Tomar, Tushar ;
Klip, Harry ;
Meersma, Gert J. ;
Hijmans, E. Marielle ;
Gennissen, Annemiek M. C. ;
Duiker, Evelien W. ;
Weening, Desiree ;
Itamochi, Hiroaki ;
Kluin, Roelof J. C. ;
Reyners, Anna K. L. ;
Birrer, Michael J. ;
Salvesen, Helga B. ;
Vergote, Ignace ;
van Nieuwenhuysen, Els ;
Brenton, James ;
Braicu, E. Ioana ;
Kupryjanczyk, Jolanta ;
Spiewankiewicz, Beata ;
Mittempergher, Lorenza ;
Bernards, Rene ;
van der Zee, Ate G. J. ;
de Jong, Steven .
CLINICAL CANCER RESEARCH, 2018, 24 (16) :3928-3940
[13]  
Chakravarty Debyani, 2017, JCO Precis Oncol, V2017, DOI 10.1200/PO.17.00011
[14]   Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling [J].
Chandler, Ronald L. ;
Damrauer, Jeffrey S. ;
Raab, Jesse R. ;
Schisler, Jonathan C. ;
Wilkerson, Matthew D. ;
Didion, John P. ;
Starmer, Joshua ;
Serber, Daniel ;
Yee, Della ;
Xiong, Jessie ;
Darr, David B. ;
de Villena, Fernando Pardo-Manuel ;
Kim, William Y. ;
Magnuson, Terry .
NATURE COMMUNICATIONS, 2015, 6
[15]   Ovarian carcinoma patient derived xenografts reproduce their tumor of origin and preserve an oligoclonal structure [J].
Colombo, Pierre-Emmanuel ;
du Manoir, Stanislas ;
Orsetti, Beatrice ;
Bras-Goncalves, Rui ;
Lambros, Mario B. ;
MacKay, Alan ;
Tien-Tuan Nguyen ;
Boissiere, Florence ;
Pourquier, Didier ;
Bibeau, Frederic ;
Reis-Filho, Jorge S. ;
Theillet, Charles .
ONCOTARGET, 2015, 6 (29) :28327-28340
[16]   Rituximab Treatment Prevents Lymphoma Onset in Gastric Cancer Patient-Derived Xenografts [J].
Corso, Simona ;
Cargnelutti, Marilisa ;
Durando, Stefania ;
Menegon, Silvia ;
Apicella, Maria ;
Migliore, Cristina ;
Capeloa, Tania ;
Ughetto, Stefano ;
Isella, Claudio ;
Medico, Enzo ;
Bertotti, Andrea ;
Sassi, Francesco ;
Sarotto, Ivana ;
Casorzo, Laura ;
Pisacane, Alberto ;
Mangioni, Monica ;
Sottile, Antonino ;
Degiuli, Maurizio ;
Fumagalli, Uberto ;
Sgroi, Giovanni ;
Molfino, Sarah ;
De Manzoni, Giovanni ;
Rosati, Riccardo ;
De Simone, Michele ;
Marrelli, Daniele ;
Saragoni, Luca ;
Rausei, Stefano ;
Pallabazzer, Giovanni ;
Roviello, Franco ;
Cassoni, Paola ;
Sapino, Anna ;
Bass, Adam ;
Giordano, Silvia .
NEOPLASIA, 2018, 20 (05) :443-455
[17]   Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models [J].
Eoh, Kyung Jin ;
Chung, Young Shin ;
Lee, So Hyun ;
Park, Sun-Ae ;
Kim, Hee Jung ;
Yang, Wookyeom ;
Lee, In Ok ;
Lee, Jung-Yun ;
Cho, Hanbyoul ;
Chay, Doo Byung ;
Kim, Sunghoon ;
Kim, Sang Wun ;
Kim, Jae-Hoon ;
Kim, Young Tae ;
Nam, Eun Ji .
CANCER RESEARCH AND TREATMENT, 2018, 50 (03) :956-963
[18]   Roles of Deletion of Arid1a, a Tumor Suppressor, in Mouse Ovarian Tumorigenesis [J].
Guan, Bin ;
Rahmanto, Yohan Suryo ;
Wu, Ren-Chin ;
Wang, Yihong ;
Wang, Zhong ;
Wang, Tian-Li ;
Shih, Ie-Ming .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2014, 106 (07)
[19]   Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies [J].
Heo, Eun Jin ;
Cho, Young Jae ;
Cho, William Chi ;
Hong, Ji Eun ;
Jeon, Hye-Kyung ;
Oh, Doo-Yi ;
Choi, Yoon-La ;
Song, Sang Yong ;
Choi, Jung-Joo ;
Bae, Duk-Soo ;
Lee, Yoo-Young ;
Choi, Chel Hun ;
Kim, Tae-Joong ;
Park, Woong-Yang ;
Kim, Byoung-Gie ;
Lee, Jeong-Won .
CANCER RESEARCH AND TREATMENT, 2017, 49 (04) :915-926
[20]   Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma [J].
Jones, Sian ;
Wang, Tian-Li ;
Shih, Ie-Ming ;
Mao, Tsui-Lien ;
Nakayama, Kentaro ;
Roden, Richard ;
Glas, Ruth ;
Slamon, Dennis ;
Diaz, Luis A., Jr. ;
Vogelstein, Bert ;
Kinzler, Kenneth W. ;
Velculescu, Victor E. ;
Papadopoulos, Nickolas .
SCIENCE, 2010, 330 (6001) :228-231