Anti-MED12 (aa 1829-1941) polyclonal antibody

Adrenocortical carcinomas (ACCs) are aggressive cancers originating in the cortex of the adrenal gland(1). Despite overall poor prognosis, ACC outcome is heterogeneous(2,3). We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes(4,5) (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs. ZNRF3, encoding a cell surface E3 ubiquitin ligase(6), was the most frequently altered gene (21%) and is a potential new tumor suppressor gene related to the beta-catenin pathway. Our integrated genomic analyses further identified two distinct molecular subgroups with opposite outcome. The C1A group of ACCs with poor outcome displayed numerous mutations and DNA methylation alterations, whereas the C1B group of ACCs with good prognosis displayed specific deregulation of two microRNA clusters. Thus, aggressive and indolent ACCs correspond to two distinct molecular entities driven by different oncogenic alterations.

The Tyrrhenian circulation, driven by the interplay of transport at its main straits and local climate, presents a marked seasonal variability. In this work we investigate the role of the horizontal resolution of the atmospheric fields in the long-term seasonal variability of the Tyrrhenian Sea circulation. We adopt the eddy-permitting ocean circulation model NEMO-MED12. Simulations cover the 1997-2008 period and are driven by atmospheric fields from PROMES regional climate model with a horizontal resolution of 50 km and 25 km. Given that this is the first time that PROMES variables have been used to run ocean simulations, we first evaluate the overall performance of this setup taking into consideration the entire model domain, which covers the whole Mediterranean Sea. We show that PROMES variables allow a good representation of the Mediterranean boundary fluxes and water masses. Focusing on the Tyrrhenian Sea, the comparison of the model results to altimeter data shows that the main features of the seasonal variability of the Tyrrhenian large-scale circulation are well captured regardless of the resolution of the atmospheric fields. However, the prescription of 25 km resolution atmospheric fields improves substantially the representation of the dynamical structures resolved by the model. Based on our results, we update intermediate-depth circulation patterns, very little studied so far. We show that changes observed with 25 km fields are not due to a better simulation of transport across Corsica, Sardinia and Sicily straits, but rather to the improved representation of winds.