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

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Effective? Locally owned? Beyond the technocratic perspective on the European Union Police Mission for the Palestinian Territories

The European Union Police Mission for the Palestinian Territories (EUPOL COPPS) was established in 2006 to contribute to the establishment of effective policing in support of an independent and democratic Palestinian state. EUPOL COPPS is often commended for its contribution to the professionalization of the Palestinian security sector under local ownership. Drawing on 40 interviews, we argue that the mission can be considered effective and locally owned only from a narrow technocratic perspective, which denies the political reality of continued occupation and absence of democracy. A broader analysis, which includes the voices of ordinary Palestinians, reveals that EUPOL COPPS contributed to the professionalization of authoritarian policing under continued Israeli occupation. Our findings show the limits of technocratic approaches to peacebuilding interventions and call for a stronger engagement with the ultimate beneficiaries of peacebuilding missions

Incorporating Socioeconomic and Political Drivers of International Collaboration into Marine Conservation Planning

International collaboration can be crucial in determining the outcomes of conservation actions. Here, we propose a framework for incorporating demographic, socioeconomic, and political data into conservation prioritization in complex regions shared by multiple countries. As a case study, we quantitatively apply this approach to one of the world's most complex and threatened biodiversity hotspots: the Mediterranean Basin. Our analysis of 22 countries surrounding the Mediterranean Sea showed that the strongest economic, trade, tourism, and political ties are clearly among the three northwestern countries of Italy, France, and Spain. Although economic activity between countries is often seen as a threat, it may also serve as an indicator of the potential of collaboration in conservation. Using data for threatened marine vertebrate species, we show how areas prioritized for conservation shift spatially when economic factors are used as a surrogate to favor areas where collaborative potential in conservation is more likely