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

Gold(I)-Catalyzed Enantioselective Synthesis of Pyrazolidines, Isoxazolidines, and Tetrahydrooxazines

Chiral ligands (L*) and chiral anions [(S)-TriPAg] are employed in the gold(I)-catalyzed enantioselective intramolecular additions of hydrazines and hydroxylamines to allenes. These complementary methods allow access to chiral vinyl isoxazolidines, oxazines, and differentially protected pyrazolidines. PNB=para-nitrobenzoy

Early incorporation of polysulphides in sedimentary organic matter

The increase in sulphur content of organic matter with depth in Recent sediments has been attributed to incorporation of either H₂S or polysulphides or to a combination of both. Indeed, the widespread occurrence of organic sulphur compounds with carbon skeletons that bear an unambiguous link with natural precursors indicates that organic matter may act as a sink for inorganic sulphur species with an efficacy second only to reactive iron minerals. Laboratory and field observations indicate that all compounds identified so far are consistent with incorporation of H₂S; molecular evidence for incorporation of polysulphides has previously been lacking. Here we report the identification of homologous series of cyclic disulphides with a linear carbon skeleton and of a cyclic di- and trisulphide with a C₂₀ isoprenoid carbon skeleton in sediments of Quaternary to Pliocene age. Although incorporation of H₂S can still explain the presence of cyclic disulphides, the cyclic trisulphide implies incorporation of inorganic polysulphides in sedimentary organic matter at the earliest stages of diagenesis