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

Impacts of climate change on marine resources in the Pacific Island region

In the Pacific Island region, marine resources make vital contributions to food security, livelihoods and economic development. Climate change is expected to have profound effects on the status and distribution of coastal and oceanic habitats, the fish and invertebrates they support and, as a result, the communities and industries that depend on these resources. To prepare for and respond to these impacts—and ensure the ongoing sustainability of marine ecosystems, and the communities and industries that rely on them economically and culturally—it is necessary to understand the main impacts and identify effective adaptation actions. In particular, declines in coral reef habitats and associated coastal fisheries productivity, more eastward distribution of tuna and impacts of more intense storms and rainfall on infrastructure are expected to present the greatest challenges for Pacific communities and economies. Some species of sharks and rays, and aquaculture commodities with calcareous shells, will also be impacted by habitat degradation, ecosystem changes, increasing temperature and ocean acidification. The projected declines in coastal fish and invertebrate populations will widen the gap between fish needed by growing human populations and sustainable harvests from coastal fisheries, with shortages expected in some nations (e.g. Papua New Guinea, Solomon Islands) by 2035. There will also be a need to diversify livelihoods based on fisheries, aquaculture and tourism because some of these operations are expected to be negatively affected by climate change. In some cases, building the resilience of Pacific communities to climate change will involve reducing dependence on, or finding alternatives, vulnerable marine resources

Impacts of climate change on marine resources in the Pacific Island region

Springer Nature Switzerland AG 2020. In the Pacific Island region, marine resources make vital contributions to food security, livelihoods and economic development. Climate change is expected to have profound effects on the status and distribution of coastal and oceanic habitats, the fish and invertebrates they support and, as a result, the communities and industries that depend on these resources. To prepare for and respond to these impacts-and ensure the ongoing sustainability of marine ecosystems, and the communities and industries that rely on them economically and culturally-it is necessary to understand the main impacts and identify effective adaptation actions. In particular, declines in coral reef habitats and associated coastal fisheries productivity, more eastward distribution of tuna and impacts of more intense storms and rainfall on infrastructure are expected to present the greatest challenges for Pacific communities and economies. Some species of sharks and rays, and aquaculture commodities with calcareous shells, will also be impacted by habitat degradation, ecosystem changes, increasing temperature and ocean acidification. The projected declines in coastal fish and invertebrate populations will widen the gap between fish needed by growing human populations and sustainable harvests from coastal fisheries, with shortages expected in some nations (e.g. Papua New Guinea, Solomon Islands) by 2035. There will also be a need to diversify livelihoods based on fisheries, aquaculture and tourism because some of these operations are expected to be negatively affected by climate change. In some cases, building the resilience of Pacific communities to climate change will involve reducing dependence on, or finding alternatives, vulnerable marine resources

B-lymphocyte tolerance and effector function in immunity and autoimmunity

B-lymphocytes are integral to host defense against microbial pathogens and are associated with many autoimmune diseases. The B-cell receptor implements B-cell self-tolerance based on the antigen specificity, and B-cell-activating factor receptor (BAFF-R) imposes homeostatic control. While shaping the repertoire, the immune tolerance process also culls mature B cells into distinct populations. The activation response of B cells is tailored to the type of pathogen attack and is facilitated by T-cell help via CD40/CD40L interaction and/or innate cell help via toll-like receptors in conjunction with BAFF receptors and ligands. Activated effector B cells not only produce antibodies, but also produce a variety of cytokines to enhance and suppress the immune response. Not surprisingly, B cells play multiple roles in both humoral and cellular immune responses during infection and autoimmune pathogenesis. Here, we discuss how gene expression and signaling networks regulate peripheral B-cell tolerance, B-cell effector functions and emerging therapies targeting B-cell signaling in autoimmune diseases