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Updated: Nov 14, 2025
Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
Secondary gliosarcoma: the clinicopathological features and the development of a patient-derived xenograft model of
Karrie Mei-Yee Kiang1, Andrian A Chan1, Gilberto Ka-Kit Leung2
1Division of Neurosurgery, Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
Background:
Gliosarcoma (GSM) is a distinct and aggressive variant of glioblastoma multiforme (GBM) with worse prognosis and few treatment options. It is often managed with the same treatment modalities with temozolomide (TMZ) as in GBM. However, the therapeutic benefits on GSM from such treatment regimen is largely unknown. Patient-derived xenograft (PDX) models have been used widely to model tumor progression, and subsequently to validate biomarkers and inform potential therapeutic regimens. Here, we report for the first time the successful development of a PDX model of secondary GSM.
Methods:
Tissue obtained from a tumor resection revealed a secondary GSM arising from GBM. The clinical, radiological, and histopathological records of the patient were retrospectively reviewed. Samples obtained from surgery were cultured ex vivo and/or implanted subcutaneously in immunocompromised mice. Histopathological features between the primary GBM, secondary GSM, and GSM PDX are compared.
Results:
In explant culture, the cells displayed a spindle-shaped morphology under phase contrast microscopy, consistent with the sarcomatous component. GSM samples were subcutaneously engrafted into immunocompromised mice after single-cell suspension. Xenografts of serial passages showed enhanced growth rate with increased in vivo passage. We did not observe any histopathological differences between the secondary GSM and its serial in vivo passages of PDX tumors.
Conclusions:
Our PDX model for GSM retained the histopathological characteristics of the engrafted tumor from the patient. It may provide valuable information to facilitate molecular and histopathological modelling of GSM and be of significant implication in future research to establish precise cancer medicine for this highly malignant tumor.
Insights
We developed a new patient-derived xenograft (PDX) model for gliosarcoma (GSM), an aggressive brain cancer. This model accurately reflects the original tumor and can help research new treatments for this rare and challenging disease.
Area of Science:
- Neuro-oncology
- Cancer biology
- Translational research
Background:
- Gliosarcoma (GSM) is an aggressive glioblastoma variant with limited treatment options.
- Current treatments for GSM often mirror those for glioblastoma multiforme (GBM), but efficacy is unclear.
- Patient-derived xenograft (PDX) models are crucial for studying tumor progression and therapeutic strategies.
Observation:
- A secondary GSM arising from GBM was identified.
- The patient's tumor was used to create a PDX model through ex vivo culture and subcutaneous implantation in mice.
- Histopathological features were compared between the primary tumor, secondary GSM, and the PDX model.
Findings:
- The PDX model cells exhibited spindle-shaped morphology, characteristic of the sarcomatous component.
- Subcutaneous engraftment in mice led to successful tumor formation.
- Serial passages in vivo demonstrated an increased growth rate without altering histopathological characteristics.
Implications:
- The developed GSM PDX model accurately retains the original tumor's histopathological features.
- This model offers a valuable platform for molecular and histopathological studies of GSM.
- It holds significant potential for advancing precision cancer medicine for this highly malignant brain tumor.
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