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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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- Sun, Q., et al.
(författare)
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Prevalence and cardiovascular risk factors of asymptomatic intracranial arterial stenosis : the Kongcun Town Study in Shandong, China
- 2020
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 27:4, s. 729-735
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose This study was to investigate the prevalence and cardiovascular risk factors (CRFs) of asymptomatic intracranial atherosclerotic stenosis (aICAS) amongst middle-aged and older adults living in rural communities in China. Methods This population-based study included 2019 subjects (aged >= 40 years, 52.3% women) who were free of stroke and living in rural communities in China. From October 2017 to May 2018, data on demographics, CRFs and health conditions were collected through face-to-face interviews, physical examination and laboratory tests. Asymptomatic ICAS was detected through a two-phase procedure: a screening phase with transcranial Doppler ultrasound, followed by a diagnostic phase with magnetic resonance angiography examination. Multivariable logistic regression models were used to analyse CRFs associated with aICAS. Results Of the 2019 participants, aICAS was detected in 153 persons. The overall prevalence of aICAS was 7.6%, and the prevalence of moderate-to-severe aICAS was 5.0%. The multi-adjusted odds ratio (95% confidence interval) of aICAS associated with CRFs was 2.40 (1.56-3.69) for hypertension, 1.91 (1.32-2.76) for high hypersensitive C-reactive protein, 1.68 (1.14-2.49) for diabetes and 1.61 (1.08-2.41) for overweight or obesity. When these four CRFs were aggregated, compared with participants without any of these factors, the multi-adjusted odds ratios (95% confidence interval) of aICAS for persons concurrently having one, two and three or more of these factors were 1.14 (0.52-2.48), 2.91 (1.42-5.99) and 5.51 (2.64-11.50), respectively (P for linear trend <0.001). Conclusions Asymptomatic ICAS is common amongst rural-dwelling middle-aged and older Chinese people. Hypertension, diabetes, overweight or obesity and high hypersensitive C-reactive protein, especially when coexisting, are strongly associated with aICAS.
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