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Updated: Aug 12, 2026
05:39
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Spatial and single-nuclei transcriptomics reveals idiosyncratic and generic patterns in papillary and anaplastic
Adrien Tourneur1, Joel Rodrigues Vitória1, Manuel Saiselet1
1IRIBHM Jacques E. Dumont, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Molecular Oncology
|August 11, 2026
Summary
BRAFV600E-mutant thyroid cancers exhibit unique tumor-specific variations. Papillary thyroid cancers (PTCs) show partial EMT, while anaplastic thyroid cancers (ATCs) undergo full EMT, offering new insights for cancer cell state classification.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- BRAFV600E mutation drives 60% of papillary thyroid cancers (PTCs), associated with significant tumor heterogeneity.
- PTCs can progress to aggressive anaplastic thyroid cancers (ATCs).
- Single-cell transcriptomics can reveal tumor heterogeneity but may be confounded by technical variations.
Purpose of the Study:
- To investigate tumor heterogeneity in BRAFV600E-mutant PTCs and ATCs.
- To disentangle biological and technical variations in single-cell RNA sequencing data.
- To propose a new classification of cancer cell states based on differentiation marker expression.
Main Methods:
- Single-nuclei RNA sequencing (snRNA-seq) and spatial transcriptomics were employed.
- An experimental design was used to separate biological and technical variations.
- Analysis focused on cancer cells and immune cell types within tumors.
Main Results:
- Significant idiosyncratic (tumor-specific) transcriptional variation was observed in cancer and immune cells, often obscured by batch integration.
- Idiosyncrasies correlated with genomic aberrations and hypoxia.
- Differentiation markers (SLC5A5, TPO, TG, TSHR) loss occurred sequentially, mirroring organoid maturation.
- PTCs showed partial epithelial-mesenchymal transition (EMT) with high FN1 expression, while ATCs exhibited full EMT and TSHR loss.
- Cancer cell microenvironments were characterized by inflammation.
Conclusions:
- Idiosyncratic variations are a key feature of BRAFV600E thyroid cancers.
- A novel classification of cancer cell states based on differentiation marker dynamics is proposed.
- Understanding these variations and cell states may aid in future stratification of BRAFV600E PTCs.
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