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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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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Bradley, KA, et al.
(författare)
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Alcohol Screening and Risk of Postoperative Complications on Male VA Patients Undergoing Major Non-cardiac Surgery
- 2011
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Ingår i: Journal of General Internal Medicine. - : Springer Science and Business Media LLC. - 0884-8734 .- 1525-1497. ; 26:2, s. 162-169
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients who misuse alcohol are at increased risk for surgical complications. Four weeks of preoperative abstinence decreases the risk of complications, but practical approaches for early preoperative identification of alcohol misuse are needed. OBJECTIVE: To evaluate whether results of alcohol screening with the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire—up to a year before surgery—were associated with the risk of postoperative complications. DESIGN: This is a cohort study. SETTING AND PARTICIPANTS: Male Veterans Affairs (VA) patients were eligible if they had major noncardiac surgery assessed by the VA’s Surgical Quality Improvement Program (VASQIP) in fiscal years 2004-2006, and completed the AUDIT-C alcohol screening questionnaire (0-12 points) on a mailed survey within 1 year before surgery. MAIN OUTCOME MEASURE: One or more postoperative complication(s) within 30 days of surgery based on VASQIP nurse medical record reviews. RESULTS Among 9,176 eligible men, 16.3% screened positive for alcohol misuse with AUDIT-C scores ≥ 5, and 7.8% had postoperative complications. Patients with AUDIT-C scores ≥ 5 were at significantly increased risk for postoperative complications, compared to patients who drank less. In analyses adjusted for age, smoking, and days from screening to surgery, the estimated prevalence of postoperative complications increased from 5.6% (95% CI 4.8–6.6%) in patients with AUDIT-C scores 1–4, to 7.9% (6.3–9.7%) in patients with AUDIT-Cs 5–8, 9.7% (6.6–14.1%) in patients with AUDIT-Cs 9–10 and 14.0% (8.9–21.3%) in patients with AUDIT-Cs 11–12. In fully-adjusted analyses that included preoperative covariates potentially in the causal pathway between alcohol misuse and complications, the estimated prevalence of postoperative complications increased significantly from 4.8% (4.1–5.7%) in patients with AUDIT-C scores 1–4, to 6.9% (5.5–8.7%) in patients with AUDIT-Cs 5-8 and 7.5% (5.0–11.3%) among those with AUDIT-Cs 9–10. CONCLUSIONS: AUDIT-C scores of 5 or more up to a year before surgery were associated with increased postoperative complications.
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