| 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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Jensen, DR, et al.
(författare)
-
Wobbling phonon excitations, coexisting with normal deformed structures in Lu-163
- 2002
-
Ingår i: Nuclear Physics, Section A. - 0375-9474. ; 703:1-2, s. 3-44
-
Tidskriftsartikel (refereegranskat)abstract
- Wobbling is a rotational mode unique to a triaxial body. The Lu-Hf isotopes with N similar to 94 at high spin provide a possible region of nuclei with pronounced triaxiality. We have investigated Lu-163 through the fusion-evaporation reaction La-139(Si-29,5n)Lu-163 with a beam energy of 152 MeV. Three excited bands decaying into the known, presumably triaxial, superdeformed (TSD) band built on the i(13/2) proton orbital are observed. The electromagnetic properties of the connecting transitions from the two strongest populated excited TSD bands have been investigated. New particle-rotor calculations in which one i(13/2) quasiproton is coupled to the core of triaxial shape produce a variety of bands, whose properties can clearly be interpreted either as "wobbling" or "cranking" motion of the core. Evidence for the assignment of the excited TSD bands as one, and possibly even two wobbling phonon modes built on the yrast TSD band in Lu-163 is given. These triaxial bands coexist with bands built on quasiparticle excitations in the normal deformed (ND) minimum for which new data are also presented.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Kupers, LK, et al.
(författare)
-
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
-
Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
|
|
| 12. |
- Linseisen, J, et al.
(författare)
-
Consumption of added fats and oils in the European Prospective Investigation into Cancer and Nutrition (EPIC) centres across 10 European countries as assessed by 24-hour dietary recalls
- 2002
-
Ingår i: Public Health Nutrition. - 1475-2727. ; 5:6B, s. 1227-1242
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the consumption of added fats and oils across the European centres and countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). Design and setting: 24-Hour dietary recalls were collected by means of standardised computer-guided interviews in 27 redefined EPIC centres across 10 European countries. Subjects: From an initial number of 36 900 subjects, single dietary recalls from 22 924 women and 13 031 men in the age range of 35-74 years were included. Results: Mean daily intake of added fats and oils varied between 16.2 g (Varese, Italy) and 41.1 g (Malmo, Sweden) in women and between 24.7 g (Ragusa, Italy) and 66.0 g (Potsdam, Germany) in men. Total mean lipid intake by consumption of added fats and oils, including those used for sauce preparation, ranged between 18.3 (Norway) and 37.2 g day(-1) (Greece) in women and 28.4 (Heidelberg, Germany) and 51.2 g day(-1) (Greece) in men. The Mediterranean EPIC centres with high olive oil consumption combined with low animal fat intake contrasted with the central and northern European centres where fewer vegetable oils, more animal fats and a high proportion of margarine were consumed. The consumption of added fats and oils of animal origin was highest in the German EPIC centres, followed by the French. The contribution of added fats and oils to total energy intake ranged from 8% in Norway to 22% in Greece. Conclusions: The results demonstrate a high variation in dietary intake of added fats Oil and oils in EPIC, providing a good opportunity to elucidate the role of dietary fats in cancer aetiology.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Um-Bergstrom, P, et al.
(författare)
-
Increased cytotoxic T-cells in the airways of adults with former bronchopulmonary dysplasia
- 2022
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 60:3
-
Tidskriftsartikel (refereegranskat)abstract
- Bronchopulmonary dysplasia (BPD) in preterm-born infants is a risk factor for chronic airway obstruction in adulthood. Cytotoxic T-cells are implicated in COPD, but their involvement in BPD is not known.ObjectivesTo characterise the distribution of airway T-cell subsets in adults with a history of BPD.MethodsYoung adults with former BPD (n=22; median age 19.6 years), age-matched adults born preterm (n=22), patients with allergic asthma born at term (n=22) and healthy control subjects born at term (n=24) underwent bronchoalveolar lavage (BAL). T-cell subsets in BAL were analysed using flow cytometry.ResultsThe total number of cells and the differential cell counts in BAL were similar among the study groups. The percentage of CD3+CD8+T-cells was higher (p=0.005) and the proportion of CD3+CD4+T-cells was reduced (p=0.01) in the BPD group, resulting in a lower CD4/CD8 ratio (p=0.007) compared to the healthy controls (median 2.2versus5.3). In BPD and preterm-born study subjects, both CD3+CD4+T-cells (rs=0.38, p=0.03) and CD4/CD8 ratio (rs=0.44, p=0.01) correlated positively with forced expiratory volume in 1 s (FEV1). Furthermore, CD3+CD8+T-cells were negatively correlated with both FEV1and FEV1/forced vital capacity (rs= −0.44, p=0.09 and rs= −0.41, p=0.01, respectively).ConclusionsYoung adults with former BPD have a T-cell subset pattern in the airways resembling features of COPD. Our findings are compatible with the hypothesis that CD3+CD8+T-cells are involved in mechanisms behind chronic airway obstruction in these patients.
|
|
| 21. |
|
|
