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

Flame retardance of epoxy acrylate resin modified with phosphorus containing compounds

In this work, UV radiation curing of allyldiphenyl phosphine oxide (ADPPO) and 4,4'-bis(allyloxyphenyl) phenyl phosphine oxide (DAPPO) monomers with epoxy acrylate resin in the presence of a photoinitiator was studied and their flame-retardant performance compared with pure epoxy acrylate film. The structures of allyl functional phosphorus compounds were characterized by FT-IR, H-1 NMR, C-13 NMR and all spectra were consistent with the expected structures. The polymerization behavior of both allyl functional monomers was followed in detail by monitoring the disappearance of acrylate and allyl groups by real-time infrared spectroscopy. It was obtained that the reactivity of DAPPO monomer is higher than ADPPO. In the case of ADPPO, chain transfer to monomer basically predominates. In each monomer, a tack free coating was obtained immediately upon irradiation. The addition of DAPPO leads to an improvement of the thermal and flame-retardant properties of the polymeric films. Thermal gravimetric analysis of DAPPO containing polymeric films gave higher char yield compared with UV cured pure epoxy acrylate resin. (C) 2004 Elsevier B.V. All rights reserved

M3: an integrative framework for structure determination of molecular machines

We present a broadly applicable, user-friendly protocol that incorporates sparse and hybrid experimental data to calculate quasi-atomic-resolution structures of molecular machines. The protocol uses the HADDOCK framework, accounts for extensive structural rearrangements both at the domain and atomic levels and accepts input from all structural and biochemical experiments whose data can be translated into interatomic distances and/or molecular shapes