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

Social Cohesion and Environmental Governance Among the Comcaac of Northern Mexico

The Comcaac have inhabited the central coast of the Sonoran Desert in Northern Mexico since time immemorial. Acknowledging the value of their continuous presence and the adaptations it has generated, scholars have documented for decades the intricacies of their environmental knowledge—a complex corpus of socio-ecological relations in constant refinement and transformation. Yet, a crucial point missing within these efforts is the recognition of the ways in which the colonial encounter and the eventual incorporation of this indigenous people into a market economy in the twentieth century drastically re-organized the ways knowledge and power flux locally—an acknowledgement that consequently challenges scholarly understandings of traditional knowledge as extemporal. As old system of reciprocity and collective accountability transformed under new forms of social organization, the individualistic inclinations that characterize the Comcaac society were drastically exacerbated by capitalist logics, producing in turn new forms of power and governance that stand at odds with previous social logics and balances. The present chapter sheds light into the existing tensions that define Comcaac livelihoods in order to better understand the social creation and transformation of environmental knowledge while reflecting upon the vulnerability and resilience that characterizes the different governance systems of the Global South dryland regions