U-CH1 Cells

The U-CH1 cell line is the first established permanent human chordoma cell model, derived from a recurrent sacral chordoma. Chordomas are rare, slow-growing, locally invasive tumors that originate from notochordal remnants and primarily occur along the axial skeleton. U-CH1 exhibits cytogenetic features characteristic of chordoma, including clonal chromosomal aberrations such as der(1)t(1;22), deletions on chromosomes 4, 5, 6, 9, 10, and 20, and a derivative chromosome 20 resulting from t(10;20). Comparative genomic hybridization revealed recurrent DNA copy number changes in chordomas, particularly losses on 1p and 3p and gains on 7q, 5q, 12q, and 20. The cytogenetic profile of U-CH1 closely mirrors that of its parental tumor, reinforcing its biological relevance.

Functionally and molecularly, U-CH1 and other chordoma cell lines display hallmark features of chordoma, including expression of brachyury, a transcription factor considered a key diagnostic marker. U-CH1 also harbors deletions of CDKN2A and lacks p16 protein expression, a recurrent genetic alteration in chordomas. This alteration leads to hyperactivation of the CDK4/6 pathway, rendering U-CH1 sensitive to CDK4/6 inhibitors such as palbociclib. Treatment with palbociclib significantly reduced phosphorylated Rb levels and inhibited proliferation in vitro, indicating that U-CH1 can be a valuable preclinical model for evaluating cell cycle-targeted therapies. The cell line has also been validated through mRNA and protein profiling, confirming its representativeness of primary chordoma tumors in expression and genomic patterns.