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

Multidetector-row CT angiography in the study of atherosclerotic carotid arteries.

Pathologies of the carotid arteries, and in particular atherosclerosis, are now an important medical problem. Stroke is the third leading cause of severe disability in the Western World leading to millions of deaths every year. Extracranial carotid atherosclerotic disease is the major risk factor for stroke. In years, with the advent of multidetector-row CT (MDCT) scanners and the use of specific angiographic protocols (MDCTA), CT imaging of the carotid arteries has become increasingly effective. In addition, the volume data obtained can be further rendered to generate high-quality two-dimensional and three-dimensional images. The purpose of this study was to review the atherosclerotic carotid arteries, their complications and how MDCTA depicts them, underlining the benefits and pitfalls of this diagnostic technique