Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma

Tyrosine kinase NTRK1 is expressed in neural and nonneuronal tissues. Like RET, NTRK1 is often activated by rearrangements that involve one of at leas t five other genes in papillary thyroid carcinoma (PTC). Because of similar ities in involvement of the two tyrosine kinases RET (rearranged during tra nsfection) and NTRK1 in the pathogenesis of PTC, the obvious parallels betw een RET and NTRK1 and between PTC and medullary thyroid carcinoma (MTC), NT RK1 seemed to be an excellent candidate gene to play a role in the genesis of MTC. Single-strand conformational polymorphism analysis of 16 exons of N TRK1, from 31 sporadic MTC, revealed variants in five exons (exons 4 and 14 -17). Sequence analysis demonstrated one sequence variant each in exons 4, 14, 16, and 17, and four different variants in exon 15. Differential restri ction enzyme digestion specific for each variant confirmed the sequencing r esults. All variants were also present in the corresponding germline DNA. I nterestingly, the sequence variants at codon 604 (c1810C>T) and codon 613 ( c1838G>T) of exon 15 always occurred together and might represent linkage d isequilibrium. The frequencies of the sequence variants in germline DNA fro m patients with sporadic MTC did not differ significantly from those in a r ace-matched control group. Although we did not find any somatic mutations o f NTRK1 in sporadic MTC, the single-strand conformational polymorphism cond itions reported here, together with the knowledge of the frequency of vario us sequence variants, may help in future mutation analyses of DNA from othe r neural and nonneural tissues.