| 1. |
- 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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| 2. |
- Abe, K., et al.
(författare)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Rapport (refereegranskat)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 3. |
- Higelin, Julia, et al.
(författare)
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NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons
- 2018
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Ingår i: Stem Cell Research. - : Elsevier. - 1873-5061 .- 1876-7753. ; 30, s. 150-162
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS). Heterozygous loss-of-function mutations in NEK1 (NIMA-related kinase 1) have also been recently found to cause ALS. NEK1 codes for a multifunctional protein, crucially involved in mitotic checkpoint control and DDR. To resolve pathological alterations associated with NEK1 mutation, we compared hiPSC-derived motoneurons carrying a NEK1 mutation with mutant C9orf72 and wild type neurons at basal level and after DNA damage induction. Motoneurons carrying a C9orf72 mutation exhibited cell specific signs of increased DNA damage. This phenotype was even more severe in NEK1c.2434A>T neurons that showed significantly increased DNA damage at basal level and impaired DDR after induction of DNA damage in an maturation-dependent manner. Our results provide first mechanistic insight in pathophysiological alterations induced by NEK1 mutations and point to a converging pathomechanism of different gene mutations causative for ALS. Therefore, our study contributes to the development of novel therapeutic strategies to reduce DNA damage accumulation in neurodegenerative diseases and ALS.
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| 4. |
- Abreu, P, et al.
(författare)
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A measurement of alpha(s) from the scaling violation in e(+)e(-) annihilation
- 1997
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 398:1-2, s. 194-206
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The hadronic fragmentation functions of the various quark flavours and of gluons are measured in a study of the inclusive hadron production from Z(0) decays with the DELPHI detector and are compared with the fragmentation functions measured elsewhere at e
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| 5. |
- Abreu, P, et al.
(författare)
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A precise measurement of the B-d(0) meson lifetime using a new technique
- 1997
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Ingår i: ZEITSCHRIFT FUR PHYSIK C-PARTICLES AND FIELDS. - : SPRINGER VERLAG. - 0170-9739. ; 74:1, s. 19-32
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- From data recorded by DELPHI between 1991 and 1994, which corresponds to 3.2 million hadronic Z(0) decays, a measurement of the <(B-d(0))over bar> meson lifetime, based on the inclusive reconstruction of 3520 +/- 150 semileptonic decays of the type <(B-d(
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| 6. |
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| 7. |
- Abreu, P, et al.
(författare)
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An upper limit for Br(Z(0)->ggg) from symmetric 3-jet Z(0) hadronic decays
- 1996
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 389:2, s. 405-415
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- An upper limit for BR(Z(0) --> 3g) is obtained from a correlation method, which distinguishes statistically between quark and gluon jets by using the difference in their charged particle multiplicity distributions. From the sample of threefold symmetric t
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| 8. |
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| 9. |
- Abreu, P, et al.
(författare)
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Identified particles in quark and gluon jets
- 1997
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 401:1-2, s. 118-130
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- A sample of about 1.4 million hadronic Z decays, selected among the data recorded by the DELPHI detector at LEP during 1994, was used to measure for the first time the momentum spectra of K+, K-0, p, Lambda and their antiparticles in gluon and quark jets.
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| 10. |
- Abreu, P, et al.
(författare)
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Kaon interference in the hadronic decays of the Z(0)
- 1996
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Ingår i: PHYSICS LETTERS B. - : ELSEVIER SCIENCE BV. - 0370-2693. ; 379:1-4, s. 330-340
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The first measurement of like-sign charged kaon correlations in hadronic decays of the Z(0) is presented, based on data collected by the DELPHI detector. The charged kaons are identified by means of ring imaging Cherenkov detectors. A significant enhancem
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