title: Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression.
abstract: DNA methylation regulates gene expression. Aberrant methylation plays an important role in human tumorigenesis. We have previously detected reduced NIS mRNA expression in thyroid tumors as compared to non-tumor tissues. Thus, in this study we investigated whether the methylation of the CpG-island located in the NIS gene promoter was associated with reduced mRNA expression in thyroid tumors. Methylation levels of 30 pairs of samples from 10 benign and 20 malignant thyroid tumors (T) along with matched non-tumor (NT) areas were determined by semiquantitative methylation specific-PCR. NIS methylation was detected in all samples. Methylation levels and frequencies did not differ between the groups and were not associated with BRAF mutational status. Highest methylation levels and frequencies were detected in the 5' region of the CpG-island decreasing toward the 3' end. Intraindividual analysis (T versus NT) showed high tumor methylation levels in 40 % of the samples in the benign group and 30 % in the malignant group, associated with low NIS mRNA expression. No quantitative correlation was detected between methylation levels and mRNA expression in any the groups. The results of this study showed that methylation of NIS promoter is a very frequent event in both benign and malignant tumors as well as in their surrounding tissues, and characterized a non-homogeneous methylation pattern along the CpG island. Therefore, further investigations involving other sites that may be implicated in methylation regulation of NIS expression are warranted.
authors.affiliation: Thyroid Unit, Cellular and Molecular Endocrine Laboratory, LIM-25, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Galrão
authors.forename: A K
authors.initials: AK
authors.lastname: Sodré
authors.forename: R Y
authors.initials: RY
authors.lastname: Camargo
authors.forename: C U
authors.initials: CU
authors.lastname: Friguglietti
authors.forename: M A
authors.initials: MA
authors.lastname: Kulcsar
authors.forename: E U
authors.initials: EU
authors.lastname: Lima
authors.forename: G
authors.initials: G
authors.lastname: Medeiros-Neto
authors.forename: I G S
authors.initials: IG
authors.lastname: Rubio
mesh_terms: D024509:3' Flanking Region; D024506:5' Flanking Region; D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D016606:Thyroid Nodule / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters