Molecular analysis of thyrotropin receptor in thyroid noeplasm

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Total RNA was prepared from 34 thyroid tisssue samples (four normal, six adenoma, six follicular cancer, and 18 papillary cancer) and reverse-transcribed into single-stranded cDNA,which was then used as a templated for the polymerase chain reaction and subjected to single-strand conformation polymorphism (SSCP) analysis. Two fragments, FRAG (468-692) (nucleotides 2044 to 2295, corresponding to the COOH-terminal, cytoplasmic dmain of the TSH-R cDNA) showed differences in electrophoretic mobility among the various thyroid tissue samples. Direct sequencing revealed Phe^<197> (TTC) * Ile (ATC), and Asp^<219> (GAT) * Glu (GAG) substitutions in FRAG (468-692) form two papillary cancers. Three types of substitution were identified in FRAG (2044-2295) : Asn^<715> (AAC) * Asp (GAC) from one papillary cancer, Lys^<723> (AAG) * Met (ATG) from one papillary cancer, and Asp^<727> (GAC) * Glu (GAG) from one normal tissue sample, one follicular cancer, and four papillary cancers. These results suggest that there exist structure changes in TSH-R in some cases of thyroid neoplastic tissue.