Activating point mutations of the gsp oncogene in human thyroid adenomas

Abstract

The gene for the alpha polypeptide chain (alpha s) of the heterotrimeric G protein Gs can be activated to the putative oncogene gsp by specific point mutations at codons 201 and 227. Such mutations have been reported in 40% of human growth hormone-secreting pituitary adenomas and in a single autonomously functioning thyroid adenoma. We examined an archival series of 45 differentiated human thyroid tumors by polymerase chain reaction amplification and oligonucleotide hybridization to identify point mutations at each of the affected codons. Successful amplification was achieved in 38 cases, and activating mutations were identified in 5 of 13 (38%) autonomously functioning adenomas, but in none of 16 nonfunctioning adenomas, six papillary carcinomas, or three follicular carcinomas. Our results confirm that the gsp oncogene is involved in the pathogenesis of autonomously functioning tumors but do not support a role in other thyroid tumors.

Similar prevalence of somatic TSH receptor and Gsα mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey

“…uni-leipzig.de/winnere and Table 1 ), and between 3 and 38% for Gsa (5,19) in different reports. In particular, studies from Japan with a very high iodine supply have reported distinctly lower frequencies for TSHR mutations in hot nodules (10,20).…”

Mutations of thyrotropin receptor isolated from thyroid autonomous functioning adenomas confer TSH-independent growth to thyroid cells

“…A molecular basis for the TSH-independent growth and function of these tumours has been recently found: some of these tumours have somatic mutations in the alpha subunit of heterotrimeric G-protein (G s a) coupled to the TSH receptor, which stimulates the adenylyl cyclase (Lyons et al, 1990;O'Sullivan et al, 1991;Suarez et al, 1991). In other cases of thyroid hyperfunctioning adenomas activating mutations of the TSH receptor have been found in the III8 intracellular loop of the receptor (Parma et al, 1993).…”

Somatic mutations of the thyroid-stimulating hormone receptor gene in feline hyperthyroidism: parallels with human hyperthyroidism

“…Activating mutations may occur in exons 1-9 in these cats; however, there have been very few mutations detected in the extracellular region of the human TSHR gene (Duprez et al 1997b, Kopp et al 1997b, Parma et al 1997, Gruters et al 1998, Biebermann et al 2000. Mutations may also occur in other genes involved in the signalling transduction pathway of the TSHR, and mutations have previously been found in a Gs subunit (a protein coupled to the TSHR) gene, in both human and feline hyperthyroidism (Lyons et al 1990, O'Sullivan et al 1991, Russo et al 1995, Parma et al 1997, Murakami et al 1999, Tonacchera et al 1999, Trulzsch et al 2001, Peeters et al 2002, Vanvooren et al 2002, Georgopoulos et al 2003.…”