Description
- Abstract:
- Background: Derived from remnant notochordal tissue, chordoma is a rare, slow-growing tumor. With the standard of care being resection and radiation, there are limited treatment options, and many patients have recurrent chordoma. Many patients with chordoma have reduced expression or loss of PTEN [Phosphatase and Tensin Homolog], a tumor suppressor that counteracts the activity of PI3K [PI3 Kinase], inactivating the signaling lipid PIP3 [Phosphatidylinositol (3,4,5)-trisphosphate] by dephosphorylating it to PIP2 [Phosphatidylinositol 4,5-bisphosphate], acting as a negative regulator of the PI3K-Akt pathway, which is one of the most mutated pathway in cancer. However, the expression status of PTEN is not yet known across chordoma cell line models and archival tissue samples from Brown’s biobank. Methods: We assessed PTEN mRNA expression using complementary assays: RNAscope (spatial ISH) and NanoString (probe-based counting) in archival FFPE chordoma tissue, and by RT-qPCR (amplification-based quantification) in cell line models. In addition, we used differential expression analysis techniques on publicly available RNA-seq datasets. Results: We found a trend of greater PTEN expression in primary chordoma relative to recurrent in both patient samples and cell lines that showed high variability. These findings suggest that the loss of PTEN expression is not universal in all chordoma cell models. Conclusions: Suggesting heterogeneity of PTEN expression within and between chordoma tumors, next is to assess possible mechanisms of reduced PTEN expression. Our current studies include (1) Sanger sequencing to evaluate disrupted coding of PTEN exons that are important regulatory sites and (2) RNA-seq data analysis within our own datasets to determine the role of non-coding RNA in PTEN regulation. Ultimately, these approaches will support understanding of whether epigenetic mechanisms contribute to the reduced expression of PTEN, with the regulation of PTEN as a potential therapeutic target for chordoma.
- Notes:
- Thesis (Sc. M.)--Brown University, 2026
Citation
Malaki, Golara,
"Multi-Omics Characterization of PTEN in Chordoma"
(2026).
Biotechnology, Biology and Medicine Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:kvb8nfpn/
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Biology and Medicine Theses and Dissertations
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