Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAF V600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAF V600E and pTERT mutations. Results: We found coexistence of pTERT C228T and BRAF V600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAF V600E positives. There was a significant association between pTERT C228T /BRAF V600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERT C228T /BRAF V600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.

BackgroundThe inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC).Patients and methodsClinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected.ResultsHOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age.ConclusionA moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.

ResumoIntrodução: o TMEM18 é um gene localizado no cromossomo 2p25.3. A recente ligação deste gene à obesidade tem sido replicada em diversos estudos de associação genômica para algumas variantes alélicas. O presente artigo analisou as frequências alélicas e genotípicas de polimorfismos no gene TMEM18 numa amostra da população de Salvador -BA, e a diferença das MAFs encontradas em relação às principais populações que respondem pela composição étnica do Brasil -ameríndios, africanos e europeus. Metodologia: participaram deste estudo 1308 crianças com idade entre 4 a 11 anos, integrantes de um estudo de coorte do projeto Social Changes, Asthmaand Allergy in LatinAmerica (SCAALA). Para a genotipagem dos indivíduos foi utilizado o painel comercial Illumina Human Omni 2, com aproximadamente 2.5 milhões de marcadores. Utilizamos os softwares PLINK (PURCELL et al., 2007) e Haploview (BROAD Institute) para controle de qualidade dos SNPs e análise de agregação de haplótipos (Linkage Desequilibrium -LD>4.2%), respectivamente. Resultados: as variantes do gene TMEM18 encontradas localizam-se na região 3´UTR (rs17729501, rs17042334, rs3187671) e intrônica (rs73153245, rs73153246, rs4241323, rs12990777, e rs2293084). Todos os polimorfismos estão em equilíbrio de Hardy-Weinberg. As frequências dos alelos menos frequentes (MAFs) observadas (9% e 9,3%) foram para os SNPs rs17729501 ers17042334, respectivamente. Os polimorfismos com as menores MAFs -s17729501 (9%) e rs17729501 (9,3%) -apresentaram, simultaneamente, as menores frequências genotípicas para homozigose, 0,5% (C/C) e 0,8% (T/T), respectivamente. As maiores taxas de heterozigose observadas na população foram de 44% (A/C -rs2293084) e 47,3% (G/A -rs12990777) e correspondem às maiores frequências alélicas (rs2293084 -34,9%; rs12990777 -47,3%). Os SNPs rs3187671, rs73153245 e rs73153246 estão em desequilíbrio de ligação. Conclusão: as frequências alélicas obtidas para os SNPs, de uma forma geral, diferiram das frequências registradas para populações de referência. O presente trabalho contribuiu com informações sobre a ocorrência de polimorfismos no TMEM18 na população brasileira, bem como com as frequências alélicas dos SNPs analisadas para os futuros estudos do tipo GWAS. Palavras-chave: Polimorfismo. Obesidade. Freqüência. Abstract Introduction: the TMEM18 is a gene located on chromosome 2p25.3. The recent connection of this gene to obesity has been replicated in several studies of genomic association to some allelic variants. This article analyzed the genotype and allele frequencies of polymorphisms in the TMEM18 gene in a sample of the population of Salvador, Bahia, and the difference of the MAFs (Minor Allele Frequency) found in relation to the main populations that account for the ethnic composition of Brazil, such as Amerindians, Africans and Europeans. Methodology: 1308 children, aged between 4 and 11 years old, participated in this study, members of a cohort study of SCAALA project (Social Changes, Asthma and Allergy in Latin America). For the genotyping of indiv...