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Non-hyperfunctioning nodules from multinodular goiters: A minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsα subunit genes

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Abstract

Constitutive activation of the cAMP pathway stimulates thyrocyte proliferation. Gainof-function mutations in Gsα protein have already been identified in thyroid nodules which have lost the ability to trap iodine. In contrast, most of the studies failed to detect somatic activating mutations in the thyrotropin receptor (TSH-R) in non-hyperfunctioning thyroid tumors. The aim of this study was to screen for mutations TSH-R exon 10, encoding the whole intracytoplasmic area involved in signal transduction, and Gsα exons 8 and 9, containing the two hot-spot codons 201 and 227, in a subset of non-hyperfunctioning nodules from multinodular goiter. Identified by matching ultrasonography and scintiscan, 22 eufunctioning (normal 99Tc uptake) and 15 nonfunctioning (decreased 99Tc uptake) nodules from 27 non-toxic multinodular goiters were isolated. After DNA extraction, TSH-R exon 10 was analyzed by direct sequencing of the PCR products and Gsα exons 8 and 9 by Denaturing Gradient Gel Electrophoresis. No mutation of TSH-R or Gsα was detected in the 37 nodules analyzed. This absence of mutation, despite the use of two sensitive screening methods associated with the analysis of the TSH-R whole intracytoplasmic area and Gsα two hot-spot codons, suggests that TSH-R and Gsα play a minor role in the pathogenesis of non-toxic nodules from multinodular goiters.

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Authors and Affiliations

  1. Department of Endocrinology, CHU, Hôpital Sud, France

    Christele Derrien, E. Sonnet, J.-Y. Poirier & D. Maugendre

  2. Department of Molecular Biology and UPR41 CNRS, Faculté de Médecine-Rennes, Rennes, France

    I. Gicquel, J.-Y. Le Gall & V. David

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  1. Christele Derrien
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  2. E. Sonnet
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  3. I. Gicquel
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  4. J.-Y. Le Gall
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  5. J.-Y. Poirier
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  6. V. David
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  7. D. Maugendre
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Correspondence to Christele Derrien.

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Derrien, C., Sonnet, E., Gicquel, I. et al. Non-hyperfunctioning nodules from multinodular goiters: A minor role in pathogenesis for somatic activating mutations in the TSH-receptor and Gsα subunit genes. J Endocrinol Invest 24, 321–325 (2001). https://doi.org/10.1007/BF03343868

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