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Updated: Mar 2, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
NGS based identification of mutational hotspots for targeted therapy in anaplastic thyroid carcinoma
Vera Tiedje1, Saskia Ting2, Thomas Herold2,3
1Department of Endocrinology and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg-Essen, Germany.
Context:
Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies.
Objective:
To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC.
Results:
In 118 ATC (57 male/ 61 female) a total of 165 mutations were found. Genes involved in the MAPK/ERK and PI3K pathway (BRAF 11.0%, HRAS 4.2%, KRAS 7.6%, NRAS 7.6%, PI3KCA 11.8%) were altered in 33%. Targetable receptor tyrosine kinases were mutated in 11%. The most frequently altered genes were TERT in 86/118 (73%) and p53 in 65/118 (55%) cases. No mutations were found analysing ALK, KIT, MET and mTOR.
Materials And Methods:
Next generation sequencing (NGS) was performed in FFPE samples from 118 ATC using MiSeq (Illumina) and CLC Cancer Research Workbench (CLCbio; Qiagen) for mutation analysis in: ALK, BRAF, CDKN2A, EGFR, ERBB2, HRAS, KIT, KRAS, MET, mTOR, NRAS, PDGFRA, PI3KCA, p53, RB1, RET and TSC2. Sanger sequencing was used to detect TERT promotor mutations.
Conclusions:
To our knowledge this is the largest study analysing mutations for targeted therapy of ATC. We found that 33% of ATC harbour mutations in pathways amendable to targeted therapy. Molecular screening in ATC is suggested for targeted therapies since current conventional treatment for ATC proved mainly futile.
Insights
Anaplastic thyroid carcinoma (ATC) has limited treatment options. This study found 33% of ATC cases harbor targetable mutations, suggesting molecular screening for personalized therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive cancer with poor outcomes.
- Conventional treatments offer limited survival benefits for ATC patients.
- Targeted therapy approaches, focusing on oncogene addiction, show promise.
Purpose of the Study:
- To investigate the prevalence of mutations in known thyroid oncogenes and signaling pathways.
- To identify potential targets for therapy in a large cohort of ATC patients.
- To assess the feasibility of targeted treatment strategies for ATC.
Main Methods:
- Next-generation sequencing (NGS) was performed on 118 ATC samples.
- Analysis included genes in MAPK/ERK, PI3K pathways, and receptor tyrosine kinases.
- TERT promoter mutations were detected using Sanger sequencing.
Main Results:
- 165 mutations were identified across 118 ATC cases.
- 33% of tumors had mutations in MAPK/ERK or PI3K pathways (e.g., BRAF, PI3KCA).
- TERT (73%) and p53 (55%) were the most frequently altered genes.
Conclusions:
- This is the largest study to date analyzing mutations for targeted therapy in ATC.
- A significant proportion (33%) of ATC cases harbor targetable mutations.
- Molecular screening is recommended for ATC patients to guide targeted therapy selection.
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