Abstract C107: Characterizing PTEN mRNA expression in patient-derived chordoma cell lines

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Abstract Chordoma is a rare, slow-growing malignant tumor originating from a remnant of the notochord. Due to chordoma growing slowly, many patients eventually develop locoregional relapse or metastatic disease, with few treatment options. Surgical removal and adjuvant radiation therapy are part of standard treatment, but chordomas are often diagnosed later in the progression. Within chordoma, reduced PTEN expression is thought of as a mechanistic biomarker due to the role of PTEN in removing the phosphate from PIP3, which ultimately reduces signaling from the Akt pathway, which promotes cancer growth (e.g., increased proliferation and cell growth). However, the expression status of PTEN across chordoma cell line models remains unclear. We assessed PTEN mRNA expression using RT-qPCR analysis of notochordal cells and various chordoma cell lines, including commercially available and institutionally biobanked patient-derived cells. Expression of PTEN mRNA was undetectable within recurrent sacrococcygeal chordoma cells (U-CH1) and notochordal (U-CH1-N) cells. However, PTEN mRNA was detectable within primary sacral chordoma cells (UCH12, JHC7, ZG1, ZG7, and ZG8). These findings indicate that the loss of PTEN expression is not universal in all chordoma cell models; there might be a shared regulatory mechanism for the cell lines that show loss of PTEN mRNA expression. These results prompt questions on whether there is an epigenetic mechanism contributing to PTEN silencing in chordoma. Our current studies include (1) Sanger sequencing to evaluate disrupted coding of PTEN exons that are important regulatory sites, (2)loss of heterozygosity analysis of exome sequencing data to detect potential deletion of a PTEN allele, and (3) RNA-seq data analysis to determine the role of non-coding RNA in PTEN regulation. Ultimately, these approaches will support understanding of whether epigenetic mechanisms contribute to the silencing of PTEN expression, with the regulation of PTEN as a potential therapeutic target for chordoma. Citation Format: Golara M. Malaki, Beatrice Campilan, Christian Godinez, Anne Antonietti, Matthew Holman, Ziya L. Gokaslan, Patricia Z. Sullivan, Margot Martinez-Moreno. Characterizing PTEN mRNA expression in patient-derived chordoma cell lines [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C107.

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