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

Safety and compatibility of magnetic-controlled growing rods and magnetic resonance imaging

PURPOSE: Magnetically controlled growth rods (MCGRs) are a new technology for the management of early-onset pediatric deformity enabling guided spinal growth by controlling the curvature. These rods contain a rare earth magnet and are contraindicated for MRI. We have investigated the behavior MCGRs to determine whether MRI adversely affects rod properties and to determine the extent of image distortion. METHODS: This is an in vitro experiment using two magnetic growth rods secured in a 1.5 T MRI. A gradient echo sequence MRI was performed to evaluate whether the rods elongated, contracted or rotated during scanning and a phantom model was used to evaluate the amount of artifact induced. RESULTS: The rod was not activated or subsequently impaired by the process of MRI. Image distortion of 28.9 cm along the long axis of the magnet and 20.1 cm perpendicular to this was seen with extension 10.6 cm cranial to the magnet housing. No negative effect was demonstrated on the magnetic rod elongation mechanism. CONCLUSIONS: This study has demonstrated that there are no detrimental effects of MRI on the MCGR and imaging of the head and neck phantom can still be interpreted. Further in vivo study is warranted