| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)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. |
- Akkoyun, S., et al.
(author)
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AGATA - Advanced GAmma Tracking Array
- 2012
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In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58
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Journal article (peer-reviewed)abstract
- The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
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| 3. |
- Hadynska-Klek, K., et al.
(author)
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Superdeformed and Triaxial States in Ca-42
- 2016
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:6
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Journal article (peer-reviewed)abstract
- Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in Ca-42 were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0(2)(+) has been obtained and the role of triaxiality in the A similar to 40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time.
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| 4. |
- Hadynska-Klek, K., et al.
(author)
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Quadrupole collectivity in Ca-42 from low-energy Coulomb excitation with AGATA
- 2018
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In: Physical Review C. - : AMER PHYSICAL SOC. - 2469-9985 .- 2469-9993. ; 97:2
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Journal article (peer-reviewed)abstract
- ACoulomb-excitation experiment to study electromagnetic properties of Ca-42 was performed using a 170-MeV calcium beam from the TANDEM XPU facility at INFN Laboratori Nazionali di Legnaro. gamma rays from excited states in Ca-42 were measured with the AGATA spectrometer. The magnitudes and relative signs of ten E2 matrix elements coupling six low-lying states in Ca-42, including the diagonal E2 matrix elements of 2(1)(+) and 2(2)(+) states, were determined using the least-squares code GOSIA. The obtained set of reduced E2 matrix elements was analyzed using the quadrupole sum rule method and yielded overall quadrupole deformation for 0(1),(+)(2) and 2(1,2)(+) states, as well as triaxiality for 0(1,2)(+) states, establishing the coexistence of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in Ca-42. The experimental results were compared with the state-of-the-art large-scale shell-model and beyond-mean-field calculations, which reproduce well the general picture of shape coexistence in Ca-42.
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| 5. |
- Hadynska-Klek, K., et al.
(author)
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Towards The Determination Of Superdeformation In Ca-42
- 2013
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In: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 44:3, s. 617-625
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Journal article (peer-reviewed)abstract
- The Coulomb excitation experiment to study electromagnetic structure of low-lying states in Ca-42 with a focus on a possible superdeformation in this nucleus was performed at the Laboratori Nazionali di Legnaro in Italy. Preliminary values of the determined quadrupole deformation parameters for both the ground state band and the presumed superdeformed band are presented.
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| 6. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 7. |
- Gottardo, A., et al.
(author)
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New Isomers in the Neutron-Rich Region Beyond 208Pb
- 2014
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In: EPJ Web of Conferences. - : EDP Sciences. - 2100-014X. - 9782759811755 - 9782759811762 ; 66, s. 02043-02043
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Conference paper (peer-reviewed)abstract
- The region of neutron-rich nuclei beyond 208Pb has been very difficult to explore due to its high mass and exoticity. However, recent experimental improvements allowed one to perform a quite extended isomer decay spectroscopy of these nuclei.
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| 8. |
- Louchart, C., et al.
(author)
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Collective nature of low-lying excitations in Zn-70,Zn-72,Zn-74 from lifetime measurements using the AGATA spectrometer demonstrator
- 2013
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:5
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Journal article (peer-reviewed)abstract
- Background: Neutron-rich nuclei with protons in the fp shell show an onset of collectivity around N=40. Spectroscopic information is required to understand the underlying mechanism and to determine the relevant terms of the nucleon-nucleon interaction that are responsible for the evolution of the shell structure in this mass region. Methods: We report on the lifetime measurement of the first 2(+) and 4(+) states in Zn-70,Zn-72 ,Zn-74 and the first 6(+) state in Zn-72 using the recoil distance Doppler shift method. The experiment was carried out at the INFN Laboratory of Legnaro with the AGATA demonstrator, first phase of the Advanced Gamma Tracking Array of highly segmented, high-purity germanium detectors coupled to the PRISMA magnetic spectrometer. The excited states of the nuclei of interest were populated in the deep inelastic scattering of a Ge-76 beam impinging on a U-238 target. Results: The maximum of collectivity along the chain of Zn isotopes is observed for Zn-72 at N=42. An unexpectedly long lifetime of 20(-5.2)(+1.8) ps was measured for the 4(+) state in Zn-74. Conclusions: Our results lead to small values of the B(E2;4(1)(+) -> 21(+))/B(E2;2(1)(+->)0(1)(+)) ratio for Zn-72,Zn-74, suggesting a significant noncollective contribution to these excitations. These experimental results are not reproduced by state-of-the-art microscopic models and call for lifetime measurements beyond the first 2(+) state in heavy zinc and nickel isotopes.
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| 9. |
- Machiela, Mitchell J., et al.
(author)
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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
- 2016
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:8, s. 1663-1676
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Journal article (peer-reviewed)abstract
- Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 x 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 x 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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| 10. |
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