Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb(-1) of root s = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s=7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb-1 of sqrt(s) = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for Contact Interactions in Dimuon Events from pp Collisions at s=7TeV\sqrt{s} = 7 TeV with the ATLAS Detector

A search for contact interactions has been performed using dimuon events recorded with the ATLAS detector in proton-proton collisions at sqrt(s) = 7 TeV. The data sample corresponds to an integrated luminosity of 42 pb-1. No significant deviation from the Standard Model is observed in the dimuon mass spectrum, allowing the following 95% C.L. limits to be set on the energy scale of contact interactions: Lambda > 4.9 TeV (4.5 TeV) for constructive (destructive) interference in the left-left isoscalar compositeness model. These limits are the most stringent to date for mumuqq contact interactions.Comment: 5 pages plus author list (18 pages total), 2 figures, 2 tables, submitted to Phys. Rev. D Rapid Communication

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in s=7\sqrt{s}=7 TeV pp\it{pp} collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb-1 of sqrt(s) = 7 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for new phenomena in events with three charged leptons at root s=7 TeV with the ATLAS detector

"A generic search for anomalous production of events with at least three charged leptons is presented. The search uses a pp-collision data sample at a center-of-mass energy of root s = 7 TeV corresponding to 4.6 fb(-1) of integrated luminosity collected in 2011 by the ATLAS detector at the CERN Large Hadron Collider. Events are required to contain at least two electrons or muons, while the third lepton may either be an additional electron or muon, or a hadronically decaying tau lepton. Events are categorized by the presence or absence of a reconstructed tau-lepton or Z-boson candidate decaying to leptons. No significant excess above backgrounds expected from Standard Model processes is observed. Results are presented as upper limits on event yields from non-Standard-Model processes producing at least three prompt, isolated leptons, given as functions of lower bounds on several kinematic variables. Fiducial efficiencies for model testing are also provided. The use of the results is illustrated by setting upper limits on the production of doubly charged Higgs bosons decaying to same-sign lepton pairs. DOI: 10.1103\/PhysRevD.87.052002