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Orthotopic Xenograft Model of Ependymoma that Maintains Genomic Signature of the Primary Tumor

ABSTRACT: The hypothesis was that the orthotopic xenograft model of ependymoma faithfully recapitulate the genomics signatures of the original tumor patient tissue

ORGANISM(S): Homo sapiens

PROVIDER: GSE17516 | GEO | 2009/08/08

SECONDARY ACCESSION(S): PRJNA118791

REPOSITORIES: GEO

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Orthotopic Xenograft Model of Ependymoma that Maintains Genomic Signature of the Primary Tumor

Project description:The hypothesis was that the orthotopic xenograft model of ependymoma faithfully recapitulate the genomics signatures of the original tumor patient tissue Original tumor cells were implanted into the same location of SCID mice and check for transcriptome profiles upon subsequent passages to show that the passages preserve the overall genomics signature of the original tumor tissue.

2009-08-08 | E-GEOD-17516 | biostudies-arrayexpress

A clinically relevant orthotopic xenograft model of ependymoma that maintains the genomic signature of the primary tumor and preserves cancer stem cells in vivo.

Project description:Limited availability of in vitro and in vivo model systems has hampered efforts to understand tumor biology and test novel therapies for ependymoma, the third most common malignant brain tumor that occurs in children. To develop clinically relevant animal models of ependymoma, we directly injected a fresh surgical specimen from a 9-year-old patient into the right cerebrum of RAG2/severe complex immune deficiency (SCID) mice. All five mice receiving the initial transplantation of the patient tumor developed intracerebral xenografts, which have since been serially subtransplanted in vivo in mouse brains for 4 generations and can be cryopreserved for long-term maintenance of tumorigenicity. The xenograft tumors shared nearly identical histopathological features with the original tumors, harbored 8 structural chromosomal abnormalities as detected with spectral karyotyping, maintained gene expression profiles resembling that of the original patient tumor with the preservation of multiple key genetic abnormalities commonly found in human ependymomas, and contained a small population (<2.2%) of CD133(+) stem cells that can form neurospheres and display multipotent capabilities in vitro. The permanent cell line (BXD-1425EPN), which was derived from a passage II xenograft tumor and has been passaged in vitro more than 70 times, expressed similar differentiation markers of the xenograft tumors, maintained identical chromosomal abnormalities, and formed tumors in the brains of SCID mice. In conclusion, direct injection of primary ependymoma tumor cells played an important role in the generation of a clinically relevant mouse model IC-1425EPN and a novel cell line, BXD-1425EPN. This cell line and model will facilitate the biological studies and preclinical drug screenings for pediatric ependymomas.

| S-EPMC2940646 | biostudies-literature

Glioblastoma Orthotopic Xenograft Transcriptome

Project description:Transcriptional profiling of glioblastoma orthotopic xenografts Descriptive experiment, comparison of 39 glioblastoma tumors as orthotopic xenografts

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Patient specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ (gene expression)

Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. Gene expression profiling experiments were conducted for 58 human glioblastoma samples using Affymetrix Human Gene 1.0 ST arrays according to manufacturer's protocol.

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Pulmonary metastasis in xenograft model after orthotopic implantation

Project description:Metastasis is a major factor for mortality in patients with hepatocellular carcinoma (HCC). Thus, there is a need for predictive biomarker(s) for detecting the tipping point before metastasis, so as to prevent further deterioration. To discover early warning signals of pulmonary metastasis in HCC, we analysed time-series gene expression data in the spontaneous pulmonary metastasis mouse HCCLM3-RFP model with our novel dynamic network biomarker (DNB) method. To simulate tumour growth and metastasis in patient livers, we used the spontaneous pulmonary metastasis mouse model, HCCLM3-RFP, which involves the orthotopic transplanted human HCCLM3 cell line labelled with a stable fluorescent protein.We observed that, hepatic tumours in orthotopic xenograft HCCLM3-RFP mice grew gradually from the second to the fifth week after orthotopic implantation in the primary liver tissue, whereas spontaneous pulmonary metastasis occurredonly at the last time point (the fifth week after orthotopic implantation).Thus, we chose the second, third, fourth, and fifth weeks after orthotopic implantation as observation points to collect liver tumours of five orthotopic xenograft mice at each time point and to assess the whole-genome expression.

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