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G protein and thyrotropin receptor mutations in thyroid neoplasia
1Department of Medicine, King's College School of Medicine and Dentistry, London, United Kingdom.
Abstract:
The cAMP pathway plays a central role in thyroid follicular cell growth and function. Mutations of the TSH receptor (TSHR) or G proteins (gsp) that activate adenylyl cyclase have been identified in autonomously functioning thyroid nodules. Gsp mutations have been identified also in other forms of thyroid neoplasia, but their reported prevalence has been extremely variable. We have studied the prevalence of gsp mutations and activating mutations of Gi2 alpha (gip) in a series of 66 benign and 34 malignant thyroid tumors. Thirty-six tumors were from Boston and 64 from the UK. In addition, we examined the 64 UK tumors for mutations of the TSHR gene. DNA extracted from fresh-frozen or paraffin-embedded tissue was amplified by PCR and examined for mutations using oligonucleotide-specific hybridization and single-strand conformation polymorphism analysis. No G protein gene mutations were identified in the Boston tumors. One gsp mutation, R201C, in a Hürthle cell adenoma and 1 gip mutation, R179C, in a follicular adenoma were demonstrated in tumors from the UK. Oligonucleotide-specific hybridization and single-strand conformation polymorphism analysis of the UK tumors did not demonstrate any mutations of the TSHR gene. Eleven normal thyroid tissue samples were wild-type for Gs alpha, Gi2 alpha, and the TSHR gene.
Insights
Activating mutations in G protein genes (gsp, gip) are rare in thyroid tumors, with only one gsp and one gip mutation found in UK samples. Thyroid stimulating hormone receptor (TSHR) gene mutations were not detected in these thyroid neoplasia.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- The cyclic adenosine monophosphate (cAMP) pathway is crucial for thyroid follicular cell growth and function.
- Activating mutations in the thyroid stimulating hormone receptor (TSHR) or G proteins (gsp) are linked to autonomously functioning thyroid nodules.
- Previous studies reported highly variable prevalence of gsp mutations in thyroid neoplasia.
Purpose of the Study:
- To investigate the prevalence of gsp and Gi2 alpha (gip) mutations in a series of benign and malignant thyroid tumors.
- To examine the 64 UK tumors for mutations in the TSHR gene.
Main Methods:
- DNA extraction from fresh-frozen or paraffin-embedded thyroid tumor tissues.
- Polymerase chain reaction (PCR) amplification followed by oligonucleotide-specific hybridization and single-strand conformation polymorphism analysis to detect mutations.
- Analysis of 66 benign and 34 malignant thyroid tumors from Boston and the UK.
Main Results:
- No G protein gene mutations were found in the 36 Boston tumors.
- One gsp mutation (R201C) was identified in a Hürthle cell adenoma from the UK.
- One gip mutation (R179C) was identified in a follicular adenoma from the UK.
- No TSHR gene mutations were detected in the 64 UK tumors.
- Eleven normal thyroid tissue samples showed wild-type sequences for Gs alpha, Gi2 alpha, and TSHR genes.
Conclusions:
- Activating mutations in G protein genes (gsp, gip) appear to be infrequent in the studied series of thyroid tumors.
- TSHR gene mutations were not found in the UK thyroid tumors examined.
- The study provides data on the prevalence of specific genetic mutations in thyroid neoplasia, contributing to understanding thyroid tumor development.