title: Mutational analysis of transforming growth factor-beta receptor type II and Smad3 tumor suppressor genes in prolactinomas.
abstract: 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.
authors: Department of Neurosurgery, Kohnan Hospital, Sendai, Japan. ikeda@nsg.med.tohoku.ac.jp
authors: Hidetoshi
authors: H
authors: Ikeda
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D019382:Human Growth Hormone / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D011388:Prolactin / Q000096:biosynthesis; D015175:Prolactinoma / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051900:Smad3 Protein / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D019382:Human Growth Hormone; D011388:Prolactin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II