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- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. 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 promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Gulin, Sofia, et al.
(author)
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Linking mass spectrometry and slab-polyacrylamide gel electrophoresis by passive elution of lipopolysaccharides from reverse-stained gels : Analysis of gel-purified lipopolysaccharides from Haemophilus influenzae strain Rd
- 2003
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 75:18, s. 4918-4924
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Journal article (peer-reviewed)abstract
- Haemophilus influenzae is an important cause of human disease, and its lipopolysaccharide (LPS) is known to be a major virulence factor. H. influenzae produces short-chain LPS of which the heterogeneity is often visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using silver staining for detection. Individual bands have not previously been recovered by this method in quantities sufficient for mass spectrometry. In an attempt toward the development of sensitive mass spectrometrical strategies to be used in structural studies of H. influenzae LPS and LPS from other bacteria, we have applied here our previously described slab-PAGE-based micropurification method to obtain unmodified LPS fractions of high purity (>95%) from a crude LPS preparation of H. influenzae strain Rd. Two LPS-fractions were obtained which, after a procedure including mild acid hydrolysis, dephosphorylation, and permethylation of the resulting oligosaccharides, were subjected to tandem electrospray ionization mass spectrometry (ESI-MS/MS). The quantities of micropurified LPS fractions-the recovery of LPS in terms of total mass was 30%-were found sufficient to allow the characterization of LPS glycoforms. The ESI-MS spectra of the individual bands showed reduced heterogeneity. Furthermore, the integrity of the micropurified LPS was confirmed. The spectra-displayed molecular ions showed improved intensity, increased respective signal-to-noise ratios demonstrating the sensitivity of analysis. Consequently, both the direct determination of the molecular masses of the gel-separated LPS glycoforms and sequence analyses using ESI-MS/MS were possible.
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