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Genetic analysis of the TSH receptor gene in differentiated human thyroid carcinomas
F Cetani1, M Tonacchera, A Pinchera
1Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Italy.
Abstract:
Somatic mutations of the TSH receptor (TSHR) gene have been identified as the major cause of toxic thyroid adenoma. Recently, point mutations of the same gene have also been described in some differentiated thyroid carcinomas. The aim of the present study was to investigate the presence TSHR gene mutations in a series of thyroid specimens obtained from 22 consecutive patients with differentiated thyroid carcinomas (8 follicular and 14 papillary). Genomic DNA was extracted from fresh-frozen or paraffin-embedded tumor and normal surrounding parenchyma. Two fragments corresponding to the entire exon 10 and one fragment corresponding to exon 9 were amplified by PCR using biotinylated primers. PCR products were purified on streptavidin-coated magnetic beads and subjected to direct sequencing with Sequenase and 35(3)-labeled d-ATP-alphaS. Adenyl-cyclase activity in membrane preparations of 10 papillary carcinomas was also determined. No TSHR mutations were detected in these tumors. A polymorphism that encoded a single amino acid change Asp727Glu was identified in two follicular thyroid carcinomas. Adenyl-cyclase activity was normal in the ten papillary thyroid carcinomas we analyzed. In conclusion, our results suggest that clonal somatic mutations of the TSHR gene do not play a role in the pathogenesis of differentiated thyroid carcinoma.
Insights
Thyroid stimulating hormone receptor (TSHR) gene mutations are not a significant cause of differentiated thyroid carcinoma. This study found no TSHR mutations in 22 thyroid cancer patients, suggesting TSHR does not drive tumor development.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Somatic mutations in the TSHR gene are a primary cause of toxic thyroid adenoma.
- TSHR gene mutations have recently been implicated in certain differentiated thyroid carcinomas.
Purpose of the Study:
- To investigate the presence of TSHR gene mutations in differentiated thyroid carcinomas.
- To determine the role of TSHR mutations in the pathogenesis of these tumors.
Main Methods:
- DNA extraction from tumor and normal thyroid tissue from 22 patients.
- PCR amplification of TSHR exons 9 and 10, followed by direct sequencing.
- Measurement of adenyl-cyclase activity in papillary carcinoma samples.
Main Results:
- No TSHR mutations were detected in any of the differentiated thyroid carcinomas analyzed.
- A polymorphism (Asp727Glu) was identified in two follicular thyroid carcinomas.
- Normal adenyl-cyclase activity was observed in papillary thyroid carcinoma samples.
Conclusions:
- Clonal somatic mutations of the TSHR gene do not appear to be a significant factor in the development of differentiated thyroid carcinoma.
- The study did not find evidence supporting TSHR as a driver mutation in these cancers.