Casa Sollievo della Sofferenza

About: Casa Sollievo della Sofferenza is a healthcare organization based out in San Giovanni Rotondo, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 2234 authors who have published 6183 publications receiving 239811 citations. The organization is also known as: Home for Relief of the Suffering.

Regulation of KEAP1 expression by promoter methylation in malignant gliomas and association with patient's outcome.

Abstract: In light with the view that KEAP1 loss of function may impact tumor behavior and modify response to chemotherapeutical agents, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC value of the curve was 0.823 (95% CI: 0.764–0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95% CI: 63–82%) and an 85% specificity (95% CI: 64–95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, p = 0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumor tissue (Spearman's Rho −0.656 p = 0.0001) and in a cell line before and after treatment with 2-deoxy-5-azacytidine (p = 0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n = 70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35–22.74). Our results further suggest that KEAP1 expression is epigenetically regulated. In addition we demonstrated that KEAP1 is frequently methylated in malignant gliomas and a predictor of patient's outcome.

A homozygous GJA1 gene mutation causes a Hallermann‐Streiff/ODDD spectrum phenotype

Abstract: Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share several clinical characteristics. However, while ODDD is a dominantly inherited disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern of the HSS syndrome is still debated. Overlapping phenotypes have been described. In one of such cases we found a homozygous change at the very conserved R76 codon (c.227G>A, p.R76H), the clinically normal parents being heterozigous carriers of the same mutation. A different base change at the same codon (p.R76S) leads to a complete dominant ODDD phenotype. A case of full-blown HSS phenotype was also analysed but GJA1 mutations were not found. GJA1 homozygous hypomorphic mutations can result in a phenotype in the HSS/ODDD spectrum. © 2004 Wiley-Liss, Inc.