Abstract
Chordomas are rare, slowly growing tumors with high medical need, arising in the axial skeleton from notochord remnants. The transcription factor “brachyury” represents a distinctive molecular marker and a key oncogenic driver of chordomas. Tyrosine kinase receptors are also expressed, but so far kinase inhibitors have not shown clear clinical efficacy in chordoma patients. The need for effective therapies is extremely high, but the paucity of established chordoma cell lines has limited preclinical research. Here we describe the isolation of the new Chor-IN-1 cell line from a recurrent sacral chordoma and its characterization as compared to other chordoma cell lines. Chor-IN-1 displays genomic identity to the tumor of origin and has morphological features, growth characteristics and chromosomal abnormalities typical of chordoma, with expression of brachyury and other relevant biomarkers. Chor-IN-1 gene variants, copy number alterations and kinome gene expression were analyzed in comparison to other four chordoma cell lines, generating large scale DNA and mRNA genomic data that can be exploited for the identification of novel pharmacological targets and candidate predictive biomarkers of drug sensitivity in chordoma. The establishment of this new, well characterized chordoma cell line provides a useful tool for the identification of drugs active in chordoma.
Highlights
Chordomas are rare, slowly growing tumors with high medical need, arising in the axial skeleton from notochord remnants
The tumor recapitulated the features of conventional chordoma, exhibiting lobulated growth of round epithelioid cells separated by fibrous septa
We focused our analysis on receptor tyrosine kinases (RTKs), which are involved in cell regulation processes and frequently dysregulated in tumors
Summary
Slowly growing tumors with high medical need, arising in the axial skeleton from notochord remnants. Chor-IN-1 gene variants, copy number alterations and kinome gene expression were analyzed in comparison to other four chordoma cell lines, generating large scale DNA and mRNA genomic data that can be exploited for the identification of novel pharmacological targets and candidate predictive biomarkers of drug sensitivity in chordoma. The establishment of this new, well characterized chordoma cell line provides a useful tool for the identification of drugs active in chordoma. Validated chordoma cell lines available from the Chordoma Foundation (a global chordoma patient advocacy group, www.chordomafoundation.org) include the prototype cell lines U-CH1 and U-CH2 and a few other more recently established cell lines[15,16,17]
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