Sequence variant in the intron 10 of the RET oncogene in a patient with microfollicular thyroid carcinoma with medullar differentiation: implications for newly generated chi-like sequence

Sequence alterations in the RET proto-oncogene are becoming increasingly important to clinical assessment of the malignant disease of the thyroid. A spectrum of mutations is necessary to establish comprehensive phenotype to genotype relationship relevant to diagnosis and therapy of thyroid malignancies. We aimed to append to the increasing database of these oncogenic lesions and, therefore, analyzed DNA from tumor tissue and constitutive DNA from a patient with thyroid carcinoma. Mutational screening and sequence characterization of the RET proto-oncogene was performed to include part of the intronic sequences. We report a germline sequence variant in DNA from the patient diagnosed with microfollicular thyroid carcinoma. The carcinoma presented not as fully developed medullar carcinoma (MTC) but as microfollicular carcinoma with tendency to evolve into MTC. We characterized the sequence variant located in the intron 10 of the RET oncogene as an A to G substitution denoted IVS10 + 4G. The described sequence alteration generates a chi-like sequence surrounded by several chi-like sequences with recombinational potential. Such alteration may be involved in the pathogenesis of the microfollicular carcinoma via genome destabilization through homologous recombination in the process of tumor progression. This result further substantiates the importance of the database correlating specific sequence variations in the RET gene with distinct disease phenotypes.