Mutational analysis of transforming growth factor-beta receptor type II and Smad3 tumor suppressor genes in prolactinomas

The presence of transforming growth factor-beta receptor type II and Smad3 gene abnormality was examined in human prolactinomas by single-strand conformation polymorphism screening for gene abnormality and band shift in tumor tissue and peripheral blood samples obtained from 14 patients treated for prolactinoma. Direct sequencing of exon 4 of the transforming growth factor-beta receptor type II gene, which showed a band shift by single-strand conformation polymorphism, disclosed a single nucleotide polymorphism (rs2228048) (alleles A/G; average allele frequency, G:0.817, A:0.183) and not an active mutation. Seven of the 14 cases showed base substitution (G → A) of the single nucleotide polymorphism. Two of these 7 cases showed base substitution (G → A) in the blood sample in accordance with neoplastic transformation. Direct sequencing of exon 2 of the Smad3 gene, which showed band shift by single-strand conformation polymorphism, disclosed single nucleotide polymorphism (rs1065080) (alleles C/T; average allele frequency, C:0.947, T:0.053) and no active mutation. Four of the 14 cases showed base substitution (C → T) of the single nucleotide polymorphism. Blood samples were available for 2 of these 4 cases, and 1 of these 2 cases showed base substitution (C → T) in accordance with neoplastic transformation. Estimation of the drug sensitivity of pituitary adenoma based on analysis of peripheral blood cells needs special care.