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

Glass transition behavior of polystyrene blocks in the cores of collapsed dry micelles tethered by poly(dimethylsiloxane) coronae in a PS-b-PDMS diblock copolymer

The micellization of a polystyrene-b-poly(dimethylsiloxane) (PS-b-PDMS) diblock copolymer with the number-average molecular weights (M-n) of 193 000 g/mol for PS block and 39 000 g/mol for PDMS block and the glass transition behavior of the PS blocks in the cores of collapsed dry micelles with PDMS tethered coronae were studied. A range of micelle morphologies was observed by varying the micellization conditions and varying the ratio of the methylene chloride (MC) solvent and the n-dodecane (D) selective nonsolvent. MC is a solvent for both of the blocks, but D is a selective solvent for only the PDMS block. After completely removing the solvents below the glass transition temperature (T-g) of the initially solvated PS blocks in MC via extraction and vacuum-drying, the collapsed dry micelles, which were originally spheres and cylinders, became "tablets" or "ribbons". The diameters of the "tablets" and widths of the "ribbons" were approximately 50 and 100 nm, respectively. The thicknesses of these textures ranged from 20 to 40 nm. The PS block cores of the dried micelles exhibited a Tg very close to that of the homo-PS bulk samples with the same M-n. However, for a broad temperature range below the T-g(PS), the collapsed dry micelles possessed heat capacity (C-p) values higher than the addition scheme calculated Cp based on PS and PDMS in their solid and liquid bulk states; whereas the C-p values of the liquid state above the T-g(PS) fit well with the calculated data. These observations support the idea of PS interface layers with mobility induced by the liquid PDMS coronae such that only the inner cores of the PS blocks were in the glassy state. In a temperature region between 0 and 50 degreesC, the lower limit of the interface thickness (i.e., assuming that the mobile PS layers possessed the same mobility as the PS liquid) was estimated to be approximately 2 nm for the collapsed dry micelles. The interface thickness slightly increased with increasing temperature