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Patient-derived xenografts of different grade gliomas retain the heterogeneous histological and genetic features of human gliomas
- Source :
- Cancer Cell International, Vol 20, Iss 1, Pp 1-12 (2020), Cancer Cell International
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Background Gliomas account for the major part of primary brain tumors. Based on their histology and molecular alternations, adult gliomas have been classified into four grades, each with distinct biology and outcome. Previous studies have focused on cell-line-based models and patient-derived xenografts (PDXs) from patient-derived glioma cultures for grade IV glioblastoma. However, the PDX of lower grade diffuse gliomas, particularly those harboring the endogenous IDH mutation, are scarce due to the difficulty growing glioma cells in vitro and in vivo. The purpose of this study was to develop a panel of patient-derived subcutaneous xenografts of different grade gliomas that represented the heterogeneous histopathologic and genetic features of human gliomas. Methods Tumor pieces from surgical specimens were subcutaneously implanted into flanks of NOD-Prkdcscid ll2rgnull mice. Then, we analyzed the association between the success rate of implantation with clinical parameters using the Chi square test and resemblance to the patient’s original tumor using immunohistochemistry, immunofluorescence, short tandem repeat analysis, quantitative real-time polymerase chain reaction, and whole-exome sequencing. Results A total of 11 subcutaneous xenografts were successfully established from 16 surgical specimens. An increased success rate of implantation in gliomas with wild type isocitrate dehydrogenase (IDH) and high Ki67 expression was observed compared to gliomas with mutant IDH and low Ki67 expression. Recurrent and distant aggressive xenografts were present near the primary implanted tumor fragments from WHO grades II to IV. The xenografts histologically represented the corresponding patient tumor and reconstituted the heterogeneity of different grade gliomas. However, increased Ki67 expression was found in propagated xenografts. Endothelial cells from mice in patient-derived xenografts over several generations replaced the corresponding human tumor blood vessels. Short tandem repeat and whole-exome sequencing analyses indicated that the glioma PDX tumors maintained their genomic features during engraftments over several generations. Conclusions The panel of patient-derived glioma xenografts in this study reproduced the diverse heterogeneity of different grade gliomas, thereby allowing the study of the growth characteristics of various glioma types and the identification of tumor-specific molecular markers, which has applications in drug discovery and patient-tailored therapy.
- Subjects :
- Cancer Research
Histology
Biology
Immunofluorescence
lcsh:RC254-282
law.invention
03 medical and health sciences
0302 clinical medicine
In vivo
law
Glioma
Genetics
medicine
Patient-derived xenografts (PDXs)
Gliomas
lcsh:QH573-671
Polymerase chain reaction
030304 developmental biology
0303 health sciences
medicine.diagnostic_test
lcsh:Cytology
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
In vitro
Isocitrate dehydrogenase
Oncology
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Heterogeneity
Primary Research
Subjects
Details
- ISSN :
- 14752867
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Cancer Cell International
- Accession number :
- edsair.doi.dedup.....51fb09bb636e698d9f1885d9b0b6239f
- Full Text :
- https://doi.org/10.1186/s12935-019-1086-5