| 1. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
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.
|
|
| 3. |
- Donahue, GS, et al.
(författare)
-
Risk factors for mid-term revision surgery in patients with articular surface replacement total hip arthroplasty
- 2018
-
Ingår i: Hip international : the journal of clinical and experimental research on hip pathology and therapy. - : SAGE Publications. - 1724-6067. ; 28:1, s. 44-49
-
Tidskriftsartikel (refereegranskat)abstract
- This study assessed the associations between gender and implant survival, as well as adverse local tissue reaction (ALTR), in patients with articular surface replacement (ASR) XL total hip arthroplasty (THA). Secondly, we sought to report the differences between genders in metal ion levels and patient reported outcome measures (PROMs) in these patients. Methods: 563 unilateral ASR XL THA patients were enrolled in a multicentre follow-up study at a mean of 6.4 years after index surgery. All patients had blood metal ion levels and PROMs obtained annually, and a valid anteroposterior pelvis radiograph. A sub-set of patients from a single centre had annual MRI performed and were analysed for the presence of moderate-to-severe ALTR. Results: 60 hips (11%) were revised during the study period. The only variables found to be associated with revision surgery in patients with unilateral THA were VAS pain (hazard ratio [HR], 1.35; p<0.001) and elevated cobalt metal ion levels (HR, 1.05; p<0.001). No variables assessed were found to be associated with prevalence of ALTR. Chromium concentrations were greater in female patients than males, while cobalt levels were similar between genders. Males reported higher HHS, EQ-5D and UCLA scores than females. Conclusions: Both males and females with metal-on-metal THA implants should be followed with equal vigilance as gender does not appear to be associated with poor outcomes, such as revision surgery and presence of ALTR.
|
|
