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- W2767987788 abstract "AbstractPatient-derived xenografts (PDXs) retain the genotype of the parental tumors more readily than tumor cells maintained in culture. In order to study the genetics of clival chordoma in the absence of prior radiation we sought to establish a PDX following the primary resection of a clival chordoma. Epicranial grafting of a primary clival chordoma was performed in NOD/SCID mice. Tumors have been passaged serially in mice for 7 generations. Physaliferous cell architecture was demonstrated in the regenerated tumors, which stained positive for Brachyury, Cytokeratin, and S100. The tumors demonstrated bone invasion. Single-nucleotide polymorphism analysis of the tumor xenograft was compared to the parental tumor. We identified homozygous amplification of the T-gene (brachury) and heterozygous loss of CDKN2A. We also identified heterozygous loss of the tumor suppressor FHIT gene, although protein expression was preserved. Accumulation of copy number losses and gains over three generations showed for the first time that there is inherent genomic instability in chordoma. In conclusion, this PDX reproduces the phenotype of clival chordoma. This study is the first to show chromosomal genomic instability in a chordoma that is serially propagated through multiple generations. The genomic instability observed in chordoma may serve as the biological basis for resistance to chemotherapy as is observed for other forms of cancer." @default.
- W2767987788 created "2017-11-17" @default.
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- W2767987788 date "2017-11-01" @default.
- W2767987788 modified "2023-09-27" @default.
- W2767987788 title "TMOD-10. MOLECULAR CHARACTERIZATION OF A NOVEL HUMAN CLIVAL CHORDOMA XENOGRAFT MODEL DEMONSTRATES INHERENT TUMOR GENOMIC INSTABILITY" @default.
- W2767987788 doi "https://doi.org/10.1093/neuonc/nox168.1049" @default.
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