ESTABLISHMENT OF PRIMARY CULTURE AND PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC GERM CELL TUMORS: PATHOLOGICAL FEATURES OF RECENTLY COLLECTED SAMPLES
- 1Hospital de Câncer de Barretos, Barretos, SP, Brazil
- 2Hospital Infantil do Câncer de Barretos, Barretos, SP, Brazil
Abstract
Introduction: Pediatric germ cell tumors (GCT) are rare neoplasms, accounting for approximately 3% of all pediatric tumors. Although most case respond well to cisplatin-based chemotherapy, refractory tumors have a poor prognosis, and personalized treatment options remain unavailable. Preclinical models are helpful in gaining insights into the molecular landscape of these tumors, predicting chemotherapy responses and revealing new potential targets for therapy. Objective: To establish primary culture and patient-derived xenograft (PDX) from pediatric patients with GCT and to describe the pathological characteristics of the collected samples. Methodology: Biological materials (blood, cerebrospinal fluid, and, when available, tumor samples) from pediatric GCTs were collected. When possible, tumor samples were processed as follows: (i) one fragment was used to establish a primary culture; (ii) another was inoculated into immunocompromised mice for development of PDX; (iii) a third was cryopreserved for further analyses. Primary cultures were routinely monitored microscopically to assess cell confluence. In PDX models, tumor growth and animal weight body weight were monitored over time. This study was approved by the Institutional Research Ethics Committee (number 2721/2024) and the Institutional Animal Care and Use Committee (number 034/2024). Results: To date, ten patients have been enrolled at Barretos Children’s Cancer Hospital, with a median age of 12 years (ranged from 1 to 18). Half of the patients were male, half were female. The most frequent histology was mature teratoma (n=5), four of which were from progressive or relapsed disease. Additional histologies included immature teratoma (n=2), germinoma (n=1), yolk sac tumor (n=1), and mixed germ cell tumor (n=1). The most common primary sites were ovary (4/10), pineal region (3/10), testis (2/10), and mediastinum (1/10). Primary cultures were attempted from five tumor samples (from different patients), resulting in the growth of cell cultures HCB-652, HCB-670, and HCB-688. PDX models were attempted from six samples, with one successful engraftment, designated OXP-56. Characterization of HCB-652 was initiated to distinguish tumor cells from fibroblasts. At passage five, RNA extraction followed by RT-PCR revealed that HCB-652 cells exhibited 3.0-fold lower VIMENTIN and POU5F1 expression, and significantly higher expression of CDH1 (31.8-fold) and SNAI2 (5.7-fold) compared with HFF-1 fibroblasts. Further analyses, including immunohistochemistry and extended RNA expression profiling, are ongoing. Conclusion: The establishment of preclinical models derived from pediatric samples provides valuable insights into GCT biology, facilitating the identification of tumor-specific characteristics and contributing to the development of novel therapeutic strategies.
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BibTeX
@article{rosa2026establishment,
title = {{ESTABLISHMENT OF PRIMARY CULTURE AND PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC GERM CELL TUMORS: PATHOLOGICAL FEATURES OF RECENTLY COLLECTED SAMPLES}},
author = {Marcela Nunes ROSA and Eleni Solange De Brito GOMES and Alexandre Ribeiro DOS REIS and Maria Alice Brangion SILVA and João Victor Neves PASCHOAL and Carlos Roberto DE ALMEIDA and Lucas Caetano Dias LOURENÇO and Sílvia Aparecida TEIXEIRA and Luiz Fernando LOPES and Rui Manuel REIS and Mariana Tomazini PINTO},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108109},
url = {https://doi.org/10.1016/j.htct.2026.108109},
note = {CC BY},
}
RIS
TY - JOUR
TI - ESTABLISHMENT OF PRIMARY CULTURE AND PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC GERM CELL TUMORS: PATHOLOGICAL FEATURES OF RECENTLY COLLECTED SAMPLES
AU - Marcela Nunes ROSA
AU - Eleni Solange De Brito GOMES
AU - Alexandre Ribeiro DOS REIS
AU - Maria Alice Brangion SILVA
AU - João Victor Neves PASCHOAL
AU - Carlos Roberto DE ALMEIDA
AU - Lucas Caetano Dias LOURENÇO
AU - Sílvia Aparecida TEIXEIRA
AU - Luiz Fernando LOPES
AU - Rui Manuel REIS
AU - Mariana Tomazini PINTO
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108109
UR - https://doi.org/10.1016/j.htct.2026.108109
AB - Introduction: Pediatric germ cell tumors (GCT) are rare neoplasms, accounting for approximately 3% of all pediatric tumors. Although most case respond well to cisplatin-based chemotherapy, refractory tumors have a poor prognosis, and personalized treatment options remain unavailable. Preclinical models are helpful in gaining insights into the molecular landscape of these tumors, predicting chemotherapy responses and revealing new potential targets for therapy. Objective: To establish primary culture and patient-derived xenograft (PDX) from pediatric patients with GCT and to describe the pathological characteristics of the collected samples. Methodology: Biological materials (blood, cerebrospinal fluid, and, when available, tumor samples) from pediatric GCTs were collected. When possible, tumor samples were processed as follows: (i) one fragment was used to establish a primary culture; (ii) another was inoculated into immunocompromised mice for development of PDX; (iii) a third was cryopreserved for further analyses. Primary cultures were routinely monitored microscopically to assess cell confluence. In PDX models, tumor growth and animal weight body weight were monitored over time. This study was approved by the Institutional Research Ethics Committee (number 2721/2024) and the Institutional Animal Care and Use Committee (number 034/2024). Results: To date, ten patients have been enrolled at Barretos Children’s Cancer Hospital, with a median age of 12 years (ranged from 1 to 18). Half of the patients were male, half were female. The most frequent histology was mature teratoma (n=5), four of which were from progressive or relapsed disease. Additional histologies included immature teratoma (n=2), germinoma (n=1), yolk sac tumor (n=1), and mixed germ cell tumor (n=1). The most common primary sites were ovary (4/10), pineal region (3/10), testis (2/10), and mediastinum (1/10). Primary cultures were attempted from five tumor samples (from different patients), resulting in the growth of cell cultures HCB-652, HCB-670, and HCB-688. PDX models were attempted from six samples, with one successful engraftment, designated OXP-56. Characterization of HCB-652 was initiated to distinguish tumor cells from fibroblasts. At passage five, RNA extraction followed by RT-PCR revealed that HCB-652 cells exhibited 3.0-fold lower VIMENTIN and POU5F1 expression, and significantly higher expression of CDH1 (31.8-fold) and SNAI2 (5.7-fold) compared with HFF-1 fibroblasts. Further analyses, including immunohistochemistry and extended RNA expression profiling, are ongoing. Conclusion: The establishment of preclinical models derived from pediatric samples provides valuable insights into GCT biology, facilitating the identification of tumor-specific characteristics and contributing to the development of novel therapeutic strategies.
SN - 2531-1379
SN - 2531-1387
ER -