Genetic and epigenetic characterization of a discordant kmt2a/aff1-rearranged infant monozygotic twin pair

The KMT2A/AFF1 rearrangement is associated with an unfavorable prognosis in infant acute lymphocytic leukemia (ALL). Discordant ALL in monozygotic twins is uncommon and represents an attractive resource to evaluate intrauterine environment–genetic interplay in ALL. Mutational and epigenetic profiles were characterized for a discordant KMT2A/AFF1-rearranged infant monozygotic twin pair and their parents, and they were compared to three independent KMT2A/AFF1-positive ALL infants, in which the DNA methylation and gene expression profiles were investigated. A de novo Q61H NRAS mutation was detected in the affected twin at diagnosis and backtracked in both twins at birth. The KMT2A/AFF1 rearrangement was absent at birth in both twins. Genetic analyses conducted at birth gave more insights into the timing of the mutation hit. We identified correlations between DNA methylation and gene expression changes for 32 genes in the three independent affected versus remitted patients. The strongest correlations were observed for the RAB32, PDK4, CXCL3, RANBP17, and MACROD2 genes. This epigenetic signature could be a putative target for the development of novel epigenetic-based therapies and could help in explaining the molecular mechanisms characterizing ALL infants with KMT2A/AFF1 fusions

Dna methylation of fkbp5 as predictor of overall survival in malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 7 10 129 ) OS-related differential methylation of a single-CpG (cg03546163), located in the 5\u2032 UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm 65 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM

Measurement of neutron yield by 62 MeV proton beam on a thick Beryllium target

In the framework of research on IVth generation reactors and high intensity neutron sources a low-power prototype neutron amplifier was recently proposed by INFN. It is based on a low-energy, high current proton cyclotron, whose beam, impinging on a thick Beryllium converter, produces a fast neutron spectrum. The world database on the neutron yield from thick Beryllium target in the 70 MeV proton energy domain is rather scarce. The new measurement was performed at LNS, covering a wide angular range from 0 to 150 degrees and an almost complete neutron energy interval. In this contribution the preliminary data are discussed together with the proposed ADS facility.Comment: Talk given by Mikhail Osipenko at the 11th International Conference on Nucleus-Nucleus Collisions (NN2012), San Antonio, Texas, USA, May 27-June 1, 2012. To appear in the NN2012 Proceedings in Journal of Physics: Conference Series (JPCS

How underground systems can contribute to meet the challenges of energy transition

The paper provides an overview of the several scientific and technical issues and challenges to be addressed for underground storage of carbon dioxide, hydrogen and mixtures of hydrogen and natural gas. The experience gained on underground energy systems and materials is complemented by new competences to adequately respond to the new needs raised by transition from fossil fuels to renewables. The experimental characterization and modeling of geological formations (including geochemical and microbiological issues), fluids and fluid-flow behavior and mutual interactions of all the systems components at the thermodynamic conditions typical of underground systems as well as the assessment and monitoring of safety conditions of surface facilities and infrastructures require a deeply integrated teamwork and fit-for-purpose laboratories to support theoretical research. The group dealing with large-scale underground energy storage systems of Politecnico di Torino has joined forces with the researchers of the Center for Sustainable Future Technologies of the Italian Institute of Technology, also based in Torino, to meet these new challenges of the energy transition era, and evidence of the ongoing investigations is provided in this paper