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Not the same thing: metastatic PTCs have a different background than ATCs.
Dario de Biase1, Federica Torricelli2, Moira Ragazzi3
1Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie) - Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, Italy.
Endocrine Connections
|November 8, 2018
Summary
Anaplastic thyroid cancer (ATC) and distant metastatic papillary thyroid cancer (DM-PTC) share TERT promoter mutations, indicating a common driver of aggressiveness. Increased mutations negatively impact survival in these aggressive thyroid cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Anaplastic thyroid cancer (ATC) is highly aggressive, while differentiated papillary thyroid cancer (PTC) rarely metastasizes.
- The genetic similarities between aggressive ATC and distantly metastatic PTC (DM-PTC) are not well-defined.
- Understanding the genetic underpinnings of thyroid cancer aggressiveness is crucial for targeted therapies.
Purpose of the Study:
- To investigate the genetic background of ATC and DM-PTC using next-generation sequencing (NGS).
- To compare the genetic profiles of aggressive thyroid cancers (ATC/DM-PTC) with non-aggressive controls (ctrl-PTC).
- To identify genetic alterations associated with thyroid cancer aggressiveness and patient survival.
Main Methods:
- Analyzed a panel of 128 amplicons across 21 thyroid cancer-related genes in 151 thyroid cancer samples.
- Utilized next-generation sequencing (NGS) for comprehensive genetic profiling.
- Performed correlation analysis to assess the impact of mutations on patient overall survival.
Main Results:
- The ATC/DM-PTC group exhibited a higher overall mutational load compared to ctrl-PTCs.
- TERT promoter mutations were significantly overrepresented in both ATC (61.1%) and DM-PTC (48.2%) compared to ctrl-PTCs (7.6%).
- In ATC, TERT promoter mutations frequently co-occurred with TP53 mutations; this was not observed in DM-PTC. MED12 mutations showed no significant association with aggressiveness.
Conclusions:
- TERT promoter mutations are a key driver of aggressiveness in both ATC and DM-PTC, suggesting a shared genetic pathway.
- Distinct genetic profiles exist between ATC and DM-PTC, despite the shared TERT promoter mutation prevalence.
- An increasing number of mutations negatively correlates with overall survival in aggressive thyroid cancer subtypes.
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