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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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- Dang, LVP, et al.
(author)
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Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam
- 2020
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In: Therapeutic advances in infectious disease. - : SAGE Publications. - 2049-9361 .- 2049-937X. ; 7, s. 2049936120958536-
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Journal article (peer-reviewed)abstract
- Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. Methods: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25–12.5) versus 50 (25–50), p < 0.01; 0 (0–0) versus 0 (0–21.43), p = 0.03 and 0 (0–7.14) versus 7.14 (7.14–7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response. Conclusion: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children.
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- Hallerstam, S, et al.
(author)
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Carotid atherosclerosis is correlated with extent and severity of coronary artery disease evaluated by myocardial perfusion scintigraphy
- 2004
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In: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 55:3, s. 281-288
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Journal article (peer-reviewed)abstract
- Increased intima-media thickness (IMT) in the common carotid artery (CCA) correlates with conventional risk factors for cardiovascular disease and is an independent predictor of cardiac events. However, correlation between IMT and degree of ischemic heart disease evaluated by coronary angiogram is weak. The purpose of this study was to investigate the relationship between measures of carotid atherosclerosis and the extent and severity of coronary artery disease (CAD) in 111 consecutive patients (60 men and 51 women, mean age 60 years) with known or suspected CAD who were investigated with adenosine-stress myocardial perfusion scintigraphy. Common carotid artery lumen diameter (LD) and IMT of the carotid bulb and distal CCA were measured with ultrasound, and CCA cross-sectional intima-media area (CIMA) was calculated. Seventy-two of 110 patients (65%) had significant perfusion defects. Increasing carotid plaque occurrence (absence, unilateral or bilateral occurrence) correlated with more advanced CAD (p<0.01). The extent and severity of myocardial hypoperfusion correlated significantly with presence of carotid plaque ( r =0.23 and 0.24 respectively, p<0.05), CIMA ( r =0.23 and 0.22, p<0.05), and LD ( r =0.26 and 0.25, p<0.01) but not with IMT. In contrast to CIMA, LD failed to show an independent relation to extent of CAD after adjustment for age, sex, and body mass index. In conclusion, in subjects with intermediate to high risk of ischemic heart disease, occurrence of carotid plaques and increased cross-sectional intima-media area in the common carotid artery are the best parameters for predicting CAD expressed as myocardial hypoperfusion.
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