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

The Effect of Repeated Physical Disturbance on Soft Tissue Decomposition?Are Taphonomic Studies an Accurate Reflection of Decomposition?

Although the relationship between decomposition and postmortem interval has been well studied, almost no studies examined the potential effects of physical disturbance occurring as a result of data collection procedures. This study compares physically disturbed rabbit carcasses with a series of undisturbed carcasses to assess the presence and magnitude of any effects resulting from repetitive disturbance. Decomposition was scored using visual assessment of soft tissue changes, and numerical data such as weight loss and carcass temperature were recorded. The effects of disturbance over time on weight loss, carcass temperature, soil pH and decomposition were studied. In addition, this study aimed to validate some of the anecdotal evidence regarding decomposition. Results indicate disturbance significantly inversely affects both weight loss and carcass temperature. No differences were apparent between groups for soil pH change or overall decomposition stage. An insect‐mediated mechanism for the disturbance effect is suggested, along with indications as to why this effect may be cancelled when scoring overall decomposition