Molecular Characterization of Putative Chordoma Cell Lines

Silke Brüderlein,Joshua B. Sommer,Sufeng Li,Peter Möller,Paul S. Meltzer,David Ng,Michael J. Kelley,David A. Alcorta,Takuya Osada

doi:10.1155/2010/630129

Silke Brüderlein, Joshua B. Sommer + Show 7 more

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https://doi.org/10.1155/2010/630129

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Abstract

Immortal tumor cell lines are an important model system for cancer research, however, misidentification and cross-contamination of cell lines are a common problem. Seven chordoma cell lines are reported in the literature, but none has been characterized in detail. We analyzed gene expression patterns and genomic copy number variations in five putative chordoma cell lines (U-CH1, CCL3, CCL4, GB60, and CM319). We also created a new chordoma cell line, U-CH2, and provided genotypes for cell lines for identity confirmation. Our analyses revealed that CCL3, CCL4, and GB60 are not chordoma cell lines, and that CM319 is a cancer cell line possibly derived from chordoma, but lacking expression of key chordoma biomarkers. U-CH1 and U-CH2 both have gene expression profiles, copy number aberrations, and morphology consistent with chordoma tumors. These cell lines also harbor genetic changes, such as loss of p16, MTAP, or PTEN, that make them potentially useful models for studying mechanisms of chordoma pathogenesis and for evaluating targeted therapies.

Highlights

IntroductionSlow-growing, and locally invasive bone tumors thought to be derived from notochordal remnants
Chordomas are rare, slow-growing, and locally invasive bone tumors thought to be derived from notochordal remnants
P-Akt β-actin β-actin paper, we report our systematic characterization of cell lines reported in the literature that claim to be of chordoma origin and establish a new chordoma cell line

Summary

Introduction

Slow-growing, and locally invasive bone tumors thought to be derived from notochordal remnants. The anatomical distribution of these tumors mirrors the location of notochord remnants, occurring most commonly at either end of the axial skeleton (32% in the clivus and 29% in the sacrum) [1]. Surgery is the mainstay of chordoma management, and radiation is commonly used as an adjuvant therapy [2]. Existing chemotherapies are usually ineffective, making management of recurrences challenging [3]. Improved systemic therapies are needed; limited knowledge of the molecular genetics of chordoma, a small patient population, and scarcity of preclinical data have hampered efforts to develop new treatments. There are only two published clinical trials of systemic therapies in chordoma; a phase II study of 9-nitro-camptothecin [4]

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