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  • Characterization of a Clival Chordoma Xenograft Model Reveals Tumor Genomic Instability.

Characterization of a Clival Chordoma Xenograft Model Reveals Tumor Genomic Instability.

The American journal of pathology (2018-09-25)
Roberto J Diaz, Amanda Luck, Andrew Bondoc, Brian Golbourn, Daniel Picard, Marc Remke, James Loukides, Nesrin Sabha, Christian Smith, Michael D Cusimano, James T Rutka
要旨

Patient-derived xenografts retain the genotype of the parent tumors more readily than tumor cells maintained in culture. The two previously reported clival chordoma xenografts were derived from recurrent tumors after radiation. To study the genetics of clival chordoma in the absence of prior radiation exposure we established a patient-derived xenograft at primary resection of a clival chordoma. Epicranial grafting of clival chordoma collected during surgery was performed. Tumor growth was established in a nonobese diabetic/severe combined immunodeficiency mouse and tumors have been passaged serially for seven generations. Physaliferous cell architecture was shown in the regenerated tumors, which stained positive for Brachyury, cytokeratin, and S100 protein. The tumors showed bone invasion. Single-nucleotide polymorphism analysis of the tumor xenograft was compared with the parental tumor. Copy number gain of the T gene (brachyury) and heterozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) was observed. Heterozygous loss of the tumor-suppressor fragile histidine triad (FHIT) gene also was observed, although protein expression was preserved. Accumulation of copy number losses and gains as well as increased growth rate was observed over three generations. The patient-derived xenograft reproduces the phenotype of clival chordoma. This model can be used in the future to study chordoma biology and to assess novel treatments.

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製品内容

Sigma-Aldrich
抗核抗体、クローン235-1, clone 235-1, Chemicon®, from mouse
Sigma-Aldrich
Anti-Brachyury Antibody, clone 3E4.2, clone 3E4.2, Upstate®, from mouse
Sigma-Aldrich
Anti-FHIT antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution