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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Paiva, D., et al.
(författare)
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Synthesis and study of the complex formation of a cationic alkyl-chain bola amino alcohol with DNA: in vitro transfection efficiency
- 2015
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Ingår i: Colloid and Polymer Science. - : Springer Science and Business Media LLC. - 1435-1536 .- 0303-402X. ; 293:11, s. 3167-3175
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies point out that bolaamphiphiles can be used in nonviral gene therapy. Due to their bipolar character, they may span a membrane and thus stabilize or destabilize it which could be relevant for DNA transfer across a biological membrane. Since there are only very few studies on bolaamphiphile application in DNA transfection, it is difficult to assess whether they will bring additional advantages to the class of nonviral vectors. A bolaamphiphile with a hydrophobic chain of 22 carbon atoms with trimethylammonium and hydroxyl groups at each end was synthesized (22-hydroxydocos-1-yl-N,N,N-trimethylammonium bromide). The bolaamphiphile conferred stability and lowered the zeta potential of vesicles of a cationic lipid. Confocal laser scanning microscopy and flow cytometry experiments have shown that this bolaamphiphile can transfect the green fluorescent protein plasmid in cells if mixed with a cationic lipid. It can compete with standard cationic lipids in terms of transfection but is at the same time less toxic. The potential of this class of molecules in gene delivery results from the fact that they will confer high stability to the DNA vector.
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