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

Perisynaptic astroglial processes: dynamic processors of neuronal information

International audienceNeuroglial interactions are now recognized as essential to brain functions. Extensive research has sought to understand the modalities of such dialog by focusing on astrocytes, the most abundant glial cell type of the central nervous system. Neuron-astrocyte exchanges occur at multiple levels, at different cellular locations. With regard to information processing, regulations occurring around synapses are of particular interest as synaptic networks are thought to underlie higher brain functions. Astrocytes morphology is tremendously complex in that their processes exceedingly branch out to eventually form multitudinous fine leaflets. The latter extremities have been shown to surround many synapses, forming perisynaptic astrocytic processes, which although recognized as essential to synaptic functioning, are poorly defined elements due to their tiny size. The current review sums up the current knowledge on their molecular and structural properties as well as the functional characteristics making them good candidates for information processing units