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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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| 4. |
- Fung, Y.L., et al.
(författare)
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Stored blood transfusion induces transient pulmonary arterial hypertension without impairing coagulation in an ovine model of nontraumatic haemorrhage.
- 2013
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Ingår i: Vox Sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 105:2, s. 150-158
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Transfusion of blood products in particular older products is associated with patient morbidity. Previously, we demonstrated a higher incidence of acute lung injury in lipopolysaccharide-treated sheep transfused with stored blood products. As transfusion following haemorrhage is more common, we aimed to determine whether a 'first hit' of isolated haemorrhage would precipitate similar detrimental effects following transfusion and also disrupt haemostasis. MATERIALS AND METHODS: Anaesthetized sheep had 33% of their total blood volume collected into Leukotrap bags (Pall Medical), which were processed into packed red blood cells and cross-matched for transfusion into other sheep. After 30 mins, the sheep were resuscitated with either: fresh (<5 days old) or stored (35-42 days old) ovine blood followed by 4% albumin to replacement volume, albumin alone or normal saline alone and monitored for 4 h. RESULTS: The first hit of haemorrhage precipitated substantial decreases in mean arterial pressure however haemostasis was preserved. Transfusion of stored ovine blood induced (1) transient pulmonary arterial hypertension but no oedema and (2) reduced fibrinogen levels more than fresh blood, but neither induced coagulopathy. Thus, transfusion of stored blood affected pulmonary function even in the absence of overt organ injury. CONCLUSION: The fact that stored blood transfusions: (1) did not induce acute lung injury in contrast to previous lipopolysaccharide-primed animal models identifies the 'first hit' as an important determinant of the severity of transfusion-mediated injury; (2) impaired pulmonary dynamics verifies the sensitivity and vulnerability of the pulmonary system to injury.
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| 5. |
- Paschke, S, et al.
(författare)
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Are Colon and Rectal Cancer Two Different Tumor Entities? A Proposal to Abandon the Term Colorectal Cancer
- 2018
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 19:9
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Tidskriftsartikel (refereegranskat)abstract
- Colon cancer (CC) and rectal cancer (RC) are synonymously called colorectal cancer (CRC). Based on our experience in basic and clinical research as well as routine work in the field, the term CRC should be abandoned. We analyzed the available data from the literature and results from our multicenter Research Group Oncology of Gastrointestinal Tumors termed FOGT to confirm or reject this hypothesis. Anatomically, the risk of developing RC is four times higher than CC, while physical activity helps to prevent CC but not RC. Obvious differences exist in molecular carcinogenesis, pathology, surgical topography and procedures, and multimodal treatment. Therefore, we conclude that CC is not the same as RC. The term “CRC” should no longer be used as a single entity in basic and clinical research as well as other areas of classification.
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