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

Herbicide Exposure and Toxicity to Aquatic Primary Producers

The aim of the present review was to give an overview of the current state of science concerning herbicide exposure and toxicity to aquatic primary producers. To this end we assessed the open literature, revealing the widespread presence of (mixtures of) herbicides, inevitably leading to the exposure of non-target primary producers. Yet, herbicide concentrations show strong temporal and spatial variations. Concerning herbicide toxicity, it was concluded that the most sensitive as well as the least sensitive species differed per herbicide and that the observed effect concentrations for some herbicides were rather independent from the exposure time. More extensive ecotoxicity testing is required, especially considering macrophytes and marine herbicide toxicity. Hence, it was concluded that the largest knowledge gap concerns the effects of sediment-associated herbicides on primary producers in the marine/estuarine environment. Generally, there is no actual risk of waterborne herbicides to aquatic primary producers. Still, median concentrations of atrazine and especially of diuron measured in China, the USA and Europe represented moderate risks for primary producers. Maximum concentrations due to misuse and accidents may even cause the exceedance of almost 60% of the effect concentrations plotted in SSDs. Using bioassays to determine the effect of contaminated water and sediment and to identify the herbicides of concern is a promising addition to chemical analysis, especially for the photosynthesis-inhibiting herbicides using photosynthesis as endpoint in the bioassays. This review concluded that to come to a reliable herbicide hazard and risk assessment, an extensive catch-up must be made concerning macrophytes, the marine environment and especially sediment as overlooked and understudied environmental compartments