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

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Patient Records and Computers An Editorial Submitted to the Annals of Internal Medicine

Improvement in clinical information-management systems is frequently cited as one strategy for coping with the cost and inefficiency of our health-care system. However, dissemination of computer-based records has been slow and fraught with logistical complications. The Institute of Medicine (IOM) recently undertook an 18-month study to examine the status of patient records and of computer-based approaches to their management. The study examined current and future users and uses of patient records plus technologies to support record automation. Strategies were then developed to address the barriers to widespread adoption of computerbased records. Solutions depend on a coordinated national, regional, and institutional approach to computing and communications infrastructure. Physicians may wish to familiarize themselves with the final report, in which the IOM has recommended that the public and private sectors join in establishing a Computer-Based Patient Record Institute to promote and f..