NOVEL MUTATIONS OF THYROTROPIN THYROID HYPERFUNCTIONING ADENOMAS - RAPID IDENTIFICATION BY FINE-NEEDLE ASPIRATION BIOPSY

Hyperfunctioning thyroid adenomas are clonal neoplasms with the intrin sic capacity of growing and differentiate independently of thyroid-sti mulating hormone (TSH). We analysed the mRNA encoding thyrotropin rece ptor of 11 adenomas obtained by fine needle aspiration biopsy (FNAB) a nd found 7 mutants all located in three aminoacids clustered in the si xth transmembrane domain of the receptor. These mutations were somatic and specifically present in the tumour tissue. DNA sequence revealed that 80 to 90% of the mutations can be rapidly screened and identified by restriction enzyme analysis of the amplified cDNA obtained from th e FNABs. The mutation Thr->Ile was introduced in the wild type recepto r and expressed in mouse fibroblasts. These cells constitutively activ ate the transcription of a reporter gene under the control of cyclic A MP responsive element.