ANALISI DI CARCINOMI PAPILLIFERI TIROIDEI MEDIANTE CGH-ARRAY

Papillary thyroid carcinoma (PTC) is the most common well differentiated thyroid tumor. By array-CGH we analysed 17 PTC (10 less aggressive and 7 more aggressive) to identified somatic copy number aberrations that may be involved in the progression and/or lethal course. Tumor DNA samples were compared to DNA samples of the same patient to identified only somatic copy number variations. Several gain or loss of genome region, present in multiple samples, have been identified. Among these, regions containing TNIK, CA12, DLEU2 and CCND3 genes were amplified in metastatic carcinomasIl carcinoma papillifero tiroideo (PTC) \ue8 il pi\uf9 comune cancro tiroideo differenziato. Mediante la metodica array-CGH abbiamo effettuato uno studio su 17 casi di PTC (10 casi poco aggressivi e 7 casi pi\uf9 aggressivi) al fine di identificare possibili alterazioni nel numero di copie geniche coinvolte nella tumorigenesi e predittive di una potenzialit\ue0 metastatica o di una trasformazione aggressiva. Il DNA tumorale \ue8 stato comparato con DNA di tessuto sano del medesimo paziente, al fine di ottenere solamente le aberrazioni cromosomiche somatiche. Sono state cos\uec identificate diverse amplificazioni e delezioni di regioni genomiche, comuni a pi\uf9 campioni analizzati. Tra queste, le regioni che comprendono i geni TNIK, CA12, DLEU2 e CCND3 risultano amplificate nei carcinomi che hanno sviluppato metastas

in thyroid cancer cell lines expression of periostin gene is controlled by p73 and is not related to epigenetic marks of active transcription

Background Periostin expression is a feature of the epithelial-mesenchymal transition, which occurs during cancer progression. Previous reports indicate that periostin expression is related to tumour aggressiveness

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities

The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines

Since PARP-1 is supposed to be part of a multimeric repressor of sodium iodide symporter (NIS) expression, in this study the effect of the PARP inhibitor PJ34 on several properties of thyroid cancer cell lines was investigated. In TPC1, BCPAP, FRO, WRO cell lines PJ34 induced a strong increase in NIS mRNA levels. In BCPAP and TPC1 cells also significant increase of radio-iodine uptake was induced. Accordingly, in transfection experiments performed in TPC1 cells, treatment with PJ34 increased NIS promoter activity without affecting PARP-1 binding to the promoter sequence. We also investigated the epigenetic status of NIS promoter after PJ34 treatment in TPC1 cell line: in addition to an increase of histone modification activation marks (H3K9K14ac, H3K4me3), surprisingly we observed also an increase of H3K27me3, a classical repressive mark. Our data demonstrate that in various thyroid cancer cell lines PARP inhibition increases NIS gene expression through a particular modulation of transcriptional regulatory mechanisms. Therefore, we suggest that PARP inhibitors may deserve future investigations as tools for medical treatment of thyroid cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved