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Summary from the GEO: "BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality."
Overall Design from the GEO: "37 tumor specimens, including 17 poorly-differentiated and 20 anaplastic thyroid cancers were expression-profiled with Affymetrix U133 plus 2.0 array."
Subject of Study
Homo sapiens
Subject(s)
Thyroid Cancer, Papillary
Thyroid Carcinoma, Anaplastic
Thyroid Neoplasms
OncoTree Cancer Type(s)
Anaplastic Thyroid Cancer
Poorly Differentiated Thyroid Cancer
Access via GEO

CEL Sequencing Data.
Accession #: GSE76039

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA307343

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus and BioProject databases provide open access to this file.
Associated Publications
Landa I, Ibrahimpasic T, Boucai L, et al. Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. Journal of Clinical Investigation. 2016; 126(3):1052-1066.
Wen S, Qu N, Ma B, et al. Cancer-Associated Fibroblasts Positively Correlate with Dedifferentiation and Aggressiveness of Thyroid Cancer. Onco Targets Ther. 2021;14:1205-1217. Published 2021 Feb 22.
Data Type
Genomic
Equipment Used
Affymetrix Human Genome U133 Plus 2.0 Array
Software Used
GEO2R

Use GEO2R to compare two or more groups of Samples in order to identify genes that are differentially expressed across experimental conditions. Results are presented as a table of genes ordered by significance.

Dataset Format(s)
TAR, CEL
Dataset Size
164.7 MB
Data Catalog Record Updated
2021-06-17