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

The Impact of Hyperoxia on Human Performance and Recovery

Abstract: Hyperoxia results from the inhalation of mixtures of gas containing higher partial pressures of oxygen (O2) than normal air at sea level. Exercise in hyperoxia affects the cardiorespiratory, neural and hormonal systems, as well as energy metabolism in humans. In contrast to short-term exposure to hypoxia (i.e. a reduced partial pressure of oxygen), acute hyperoxia may enhance endurance and sprint interval performance by accelerating recovery processes. This narrative literature review, covering 89 studies published between 1975 and 2016, identifies the acute ergogenic effects and health concerns associated with hyperoxia during exercise; however, long-term adaptation to hyperoxia and exercise remain inconclusive. The complexity of the biological responses to hyperoxia, as well as the variations in (1) experimental designs (e.g. exercise intensity and modality, level of oxygen, number of participants), (2) muscles involved (arms and legs) and (3) training status of the participants may account for the discrepancies.First Online: 30 July 2016</p