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

Great Britain: the intertidal and underwater archaeology of Britain’s submerged landscapes

The submerged landscapes around Great Britain are extensive and would have offered productive territory for hunting, gathering, exploitation of aquatic and marine resources, and—in the final stages of postglacial sea-level rise—opportunities for agriculture. They would also have provided land connections to continental Europe and opportunities for communication by sea travel along now-submerged palaeocoastlines and river estuaries. Most of the archaeological material has been discovered in intertidal or shallow water conditions, but there are also discoveries in deeper water, with dates ranging from earliest human presence nearly one million years ago up to the establishment of modern sea level. Some later material is present where coastlines have continued to sink in more recent millennia. Intertidal sites are especially well represented because of relatively large tidal ranges and shallow offshore gradients on many coastlines. These are often associated with remains of submerged forests, which are periodically exposed at low tide and then covered up again by movements of sand. Some of the most distinctive intertidal finds are the human and animal footprints preserved in intertidal sediments in many locations, especially at Goldcliff East. The earliest, at Happisburgh, are dated between 0.78 and 1 Ma. Fully submerged sites include the Mesolithic site of Bouldnor Cliff with its worked timbers, and the Middle Stone Age artefacts from offshore aggregate Area 240 along with well-preserved ice age fauna and environmental indicators. Pioneering work using oil industry seismic records has produced detailed reconstructions of the submerged landscape, and this is being followed up by new work involving targeted acoustic survey and coring of sediments