ANALYSIS OF THYROID-STIMULATING HORMONE-RECEPTOR MUTATIONS BY TEMPERATURE-GRADIENT GEL-ELECTROPHORESIS

Somatic mutations in the genes for G-protein-coupled receptors which r egulate intracellular levels of cyclic AMP have been found in several regions coding for the receptors of melanocyte-stimulating hormone, ad renaline, luteinizing hormone, rhodopsin and thyrotropin. The mutation s found in the thyroid-stimulating hormone (TSH) receptor are restrict ed to cells of hyperfunctioning thyroid adenomas and other thyroid tum ors. They are thought to lead to a constitutive activation of the rece ptor independent of TSH. We have developed a temperature-gradient gel electrophoresis (TGGE) assay starting with the amplification of a part of exon 10 of the TSH-receptor gene to screen tissue of thyroid tumou rs. TGGE allows the detection of point mutations even if there are onl y a few cells with somatic mutations in tissue sections.