- Title Information
- Title
- Transcriptomic Characterization of Chordoma with Functional Investigation of ErbB Signaling and Early-Stage 3D Organoid Optimization
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Shin, Leah
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Sullivan, Patricia
- Role
- Role Term:
Text
- Advisor
- Name:
Personal
- Name Part
- Martinez-Moreno, Margot
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Crego, Adam
- Role
- Role Term:
Text
- Reader
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2026
- Physical Description
- Extent
- 9, 69 p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2026
- Genre (aat)
- theses
- Abstract
- Chordoma is a rare cancer of notochordal origin with frequent recurrence and limited treatment options. To better understand recurrence-associated changes and oncogenesis in chordoma, this study combined transcriptomic analysis, ErbB signaling experiments, and early 3D organoid optimization. Existing bulk RNA-seq and NanoString datasets comparing primary and recurrent chordoma were analyzed, and additional bulk RNA-seq comparing primary chordoma with disc tissue was performed. Then ErbB signaling was examined in recurrent chordoma-derived MUG-Chor1 cells using siRNA targeting ERBB2 and EGR2, followed by qPCR and Western blot. Initial organoid experiments were conducted using chordoma-derived cell lines under suspension and Matrigel-based conditions with different supplements.
Bulk RNA-seq identified transcriptomic differences between primary vs recurrent chordoma, and NanoString data supported recurrence-associated changes in progression and immune programs. The progression panel highlighted altered growth and proliferation pathways, including PI3K-AKT/ErbB signaling. The immune panel showed higher expression of inflammatory and cytokine-related genes, including EGR2 in recurrent samples. Primary chordoma vs disc tissue analysis also demonstrated a distinct transcriptional profile, with stronger enrichment of stress-adaptive metaprograms in chordoma, whereas disc tissue was more enriched for fibroblast, stromal, remodeling, and matrix-related programs. In MUG-Chor1 cells, ERBB2-targeting siRNA reduced ERBB2 transcript and protein levels and decreased EGR2 transcript expression, although clear EGR2 protein reduction was not observed. PKI-166 treatment likewise reduced ERBB2 and EGR2 transcript expression, while stronger protein-level effects were observed in decreased AKT and ERK phosphorylation with reduced cell viability and proliferation. During organoid optimization, collagen-containing matrix conditions supported denser cell aggregation and growth compared with Matrigel-only conditions.
Together, these findings identify recurrent chordoma as a distinct molecular state, support the ErbB axis as a plausible therapeutic target, and suggest that extracellular matrix context may influence chordoma cell behavior. The study also provides a preliminary foundation for future 3D chordoma organoid development.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00858592")
- Topic
- Chordoma
- Subject
- Topic
- Organoid
- Subject
- Topic
- ErbB
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20260516