The Impact of Olfactory Disorders in the United Kingdom

Olfactory disorders are believed to affect 5% of the general population and have been shown to bear significant psychosocial consequences to sufferers. Although more common than blindness and profound deafness in the United Kingdom, the impact of these disorders has not been assessed to date and the plight of British patients has yet to be quantified. In 2012, a patient support organization, Fifth Sense, was founded to provide information and support to sufferers of chemosensory disorders. Following a recent members conference, a survey of the membership was conducted anonymously using a series of questions based on an existing olfactory disorders questionnaire. From 496 respondents, this has demonstrated high rates of depression (43%) and anxiety (45%), impairment of eating experience (92%), isolation (57%), and relationship difficulties (54%). Women appear to have significantly more issues than men in terms of social and domestic dysfunction relating to olfactory loss (P = 0.01). Qualitative disorders also affected more than 1 in 5 members with parosmia reported in 19% and phantosmia in 24%. This paper discusses the details of the British story of anosmia and other related disorders as depicted by those most affected

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