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

Voluntary cognitive screening: characteristics of participants in an Asian setting

Vanda Ho,1,2 Nur Hani Zainal,1 Linda Lim,1 Aloysius Ng,1 Eveline Silva,1 Nagaendran Kandiah1,3 1Department of Neurology, National Neuroscience Institute, Singapore; 2School of Clinical Medicine, University of Cambridge, Cambridge, UK; 3Duke-NUS Graduate Medical School, Singapore Background: Mild cognitive impairment (MCI) and dementia are reaching epidemic proportions in Asia. Lack of awareness and late presentation are major obstacles to early diagnosis and timely intervention. Cognitive screening may be an effective method for early detection of dementia in Asia. The purpose of this work was to study the characteristics of subjects volunteering for cognitive screening in an Asian setting and to determine the prevalence of MCI.Methods: Retrospective and cross-sectional data from community subjects attending a screening program from 2008 to 2013 were analyzed. Information on demographics, vascular risk factors, subjective symptoms, and cognitive measures were analyzed over the 6-year period.Results: Over the 6 years from 2008 to 2013, 1,243 community subjects voluntarily turned up for cognitive screening (91.2% were Chinese, 5.23% were Indian, 1.37% were Malay, and 2.25% were Eurasian). The mean age of the participants was 61.3 years and the mean number of years of education was 11.0 years. A total of 71.1% of participants were living in public housing, 59.8% had at least one cardiovascular risk factor, and 56.2% reported subjective cognitive symptoms. Over a period of 6 years, no significant change in demographic or clinical variables was noted. High cholesterol and hypertension were consistently the top two risk factors found in the population screened. In total, 17.2% of the total cohort had MCI. Across the 6 years, the proportion with MCI and depression was relatively constant.Conclusion: A significant proportion of participants attending voluntary cognitive screening have MCI. Low level of education and presence of vascular risk factors are general predisposing characteristics for MCI, and there are more specific factors pertaining to sex and employment status. Keywords: early detection, screening, cognitive impairment, dementia, vascular risk factor