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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. |
- Mac, TH, et al.
(författare)
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Optimizing Active Tuberculosis Case Finding: Evaluating the Impact of Community Referral for Chest X-ray Screening and Xpert Testing on Case Notifications in Two Cities in Viet Nam
- 2020
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Ingår i: Tropical medicine and infectious disease. - : MDPI AG. - 2414-6366. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- To accelerate the reduction in tuberculosis (TB) incidence, it is necessary to optimize the use of innovative tools and approaches available within a local context. This study evaluated the use of an existing network of community health workers (CHW) for active case finding, in combination with mobile chest X-ray (CXR) screening events and the expansion of Xpert MTB/RIF testing eligibility, in order to reach people with TB who had been missed by the current system. A controlled intervention study was conducted from January 2018 to March 2019 in five intervention and four control districts of two low to medium TB burden cities in Viet Nam. CHWs screened and referred eligible persons for CXR to TB care facilities or mobile screening events in the community. The initial diagnostic test was Xpert MTB/RIF for persons with parenchymal abnormalities suggestive of TB on CXR or otherwise on smear microscopy. We analyzed the TB care cascade by calculating the yield and number needed to screen (NNS), estimated the impact on TB notifications and conducted a pre-/postintervention comparison of TB notification rates using controlled, interrupted time series (ITS) analyses. We screened 30,336 individuals in both cities to detect and treat 243 individuals with TB, 88.9% of whom completed treatment successfully. All forms of TB notifications rose by +18.3% (95% CI: +15.8%, +20.8%). The ITS detected a significant postintervention step-increase in the intervention area for all-form TB notification rates (IRR(β6) = 1.221 (95% CI: 1.011, 1.475); p = 0.038). The combined use of CHWs for active case findings and mobile CXR screening expanded the access to and uptake of Xpert MTB/RIF testing and resulted in a significant increase in TB notifications. This model could serve as a blueprint for expansion throughout Vietnam. Moreover, the results demonstrate the need to optimize the use of the best available tools and approaches in order to end TB.
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