GEO series

Mitochondrial DNA Mutations Drive Tumor Heterogeneity in Papillary Thyroid Carcinoma

GSE317520 Homo sapiens Expression profiling by high throughput sequencing; Other 92 samples Submitted 2026/07/15 Platform GPL24676

Summary

Tumor heterogeneity presents a major challenge to understanding cancer evolution and therapeutic resistance in thyroid cancer. While previous studies have focused on nuclear driver mutations, the role of mitochondrial DNA (mtDNA) alterations in this heterogeneity remains elusive. Through multi-regional whole-genome and transcriptome sequencing of aggressive papillary thyroid carcinoma (PTC), we reveal that mtDNA mutations exhibit significant spatial and evolutionary heterogeneity, contrasting with conserved nuclear drivers. High mtDNA mutation burden correlated with increased mitochondrial gene expression, tumor dedifferentiation, and immune pathway activation via damage-associated molecular pattern signaling. This burden further remodeled the tumor microenvironment, favoring pro-inflammatory epithelial states over normal stromal populations. Clinically, these features were associated with reduced disease-free survival. Our findings identify mtDNA mutations as key drivers of heterogeneity and immune remodeling in PTC, suggesting mitochondrial mutational burden as a potential prognostic biomarker and therapeutic target.

Published in

Mitochondrial DNA mutations drive tumor heterogeneity in papillary thyroid carcinoma

Lee HS, Lim J, Heo JH et al. · iScience 2026 · PMID 42436980 · doi:10.1016/j.isci.2026.116361

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Direct links to NCBI, no account and no request form: the whole study as GSE317520_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 92 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1414416. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42436980) ↗

Study design

40 conditions, each sampled once — no replicated groups

Read from the first 40 of 92 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.

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