The Consensus Molecular Subtypes of Colorectal Cancer

Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use -- https://www.nature.com/authors/policies/license.html#termsColorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC - with clear biological interpretability - and the basis for future clinical stratification and subtype-based targeted interventions

Electroweak parameters of the z0 resonance and the standard model

Contains fulltext : 124399.pdf (publisher's version ) (Open Access

A panoply of errors: polymerase proofreading domain mutations in cancer

Although it has long been recognized that the exonucleolytic proofreading activity intrinsic to the replicative DNA polymerases Pol δ and Pol ε is essential for faithful replication of DNA, evidence that defective DNA polymerase proofreading contributes to human malignancy has been limited. However, recent studies have shown that germline mutations in the proofreading domains of Pol δ and Pol ε predispose to cancer, and that somatic Pol ε proofreading domain mutations occur in multiple sporadic tumours, where they underlie a phenotype of 'ultramutation' and favourable prognosis. In this Review, we summarize the current understanding of the mechanisms and consequences of polymerase proofreading domain mutations in human malignancies, and highlight the potential utility of these variants as novel cancer biomarkers and therapeutic targets

Design and performance of the ABCD3TA ASIC for readout of silicon strip detectors in the ATLAS semiconductor tracker

The ABCD3TA is a 128-channel ASIC with binary architecture for the readout of silicon strip particle detectors in the Semiconductor Tracker of the ATLAS experiment at the Large Hadron Collider (LHC). The chip comprises fast front-end and amplitude discriminator circuits using bipolar devices, a binary pipeline for first level trigger latency, a second level derandomising buffer and data compression circuitry based on CMOS devices. It has been designed and fabricated in a BiCMOS radiation resistant process. Extensive testing of the ABCD3TA chips assembled into detector modules show that the design meets the specifications and maintains the required performance after irradiation up to a total ionising dose of 10 Mrad and a 1-MeV neutron equivalent fluence of 2×1014 n/cm2, corresponding to 10 years of operation of the LHC at its design luminosity. Wafer screening and quality assurance procedures have been developed and implemented in large volume production to ensure that the chips assembled into modules meet the rigorous acceptance criteria.</p