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

Survey of current perspectives on consumer-available digital health devices for detecting atrial fibrillation.

Background: Many digital health technologies capable of atrial fibrillation (AF) detection are directly available to patients. However, adaptation into clinical practice by heart rhythm healthcare practitioners (HCPs) is unclear. Objective: To examine HCP perspectives on use of commercial technologies for AF detection and management. Methods: We created an electronic survey for HCPs assessing practice demographics and perspectives on digital devices for AF detection and management. The survey was distributed electronically to all members of 3 heart rhythm professional societies. Results: We received 1601 responses out of 73,563 e-mails sent, with 43.6% from cardiac electrophysiologists, 12.8% from fellows, and 11.6% from advanced practice practitioners. Most respondents (62.3%) reported having recommended patient use of a digital device for AF detection. Those who did not had concerns about their accuracy (29.6%), clinical utility of results (22.8%), and integration into electronic health records (19.8%). Results from a 30-second single-lead electrocardiogram were sufficient for 42.7% of HCPs to recommend oral anticoagulation for patients at high risk for stroke. Respondents wanted more data comparing the accuracy of digital devices to conventional devices for AF monitoring (64.9%). A quarter (27.3%) of HCPs had no reservations recommending digital devices for AF detection, and most (53.4%) wanted guidelines from their professional societies providing guidance on their optimal use. Conclusion: Many HCPs have already integrated digital devices into their clinical practice. However, HCPs reported facing challenges when using digital technologies for AF detection, and professional society recommendations on their use are needed