| 1. |
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| 2. |
- 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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| 3. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 4. |
- Rodriguez-Martin, B, et al.
(författare)
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Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 306-
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Tidskriftsartikel (refereegranskat)abstract
- About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of 22 L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors.
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| 5. |
- Akdemir, KC, et al.
(författare)
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Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 294-
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Tidskriftsartikel (refereegranskat)abstract
- Chromatin is folded into successive layers to organize linear DNA. Genes within the same topologically associating domains (TADs) demonstrate similar expression and histone-modification profiles, and boundaries separating different domains have important roles in reinforcing the stability of these features. Indeed, domain disruptions in human cancers can lead to misregulation of gene expression. However, the frequency of domain disruptions in human cancers remains unclear. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumor types, we analyzed 288,457 somatic structural variations (SVs) to understand the distributions and effects of SVs across TADs. Notably, SVs can lead to the fusion of discrete TADs, and complex rearrangements markedly change chromatin folding maps in the cancer genomes. Notably, only 14% of the boundary deletions resulted in a change in expression in nearby genes of more than twofold.
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| 6. |
- Cortes-Ciriano, I, et al.
(författare)
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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
- 2020
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 52:3, s. 331-
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Tidskriftsartikel (refereegranskat)abstract
- Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.
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| 7. |
- Li, YL, et al.
(författare)
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Patterns of somatic structural variation in human cancer genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- A key mutational process in cancer is structural variation, in which rearrangements delete, amplify or reorder genomic segments that range in size from kilobases to whole chromosomes1–7. Here we develop methods to group, classify and describe somatic structural variants, using data from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), which aggregated whole-genome sequencing data from 2,658 cancers across 38 tumour types8. Sixteen signatures of structural variation emerged. Deletions have a multimodal size distribution, assort unevenly across tumour types and patients, are enriched in late-replicating regions and correlate with inversions. Tandem duplications also have a multimodal size distribution, but are enriched in early-replicating regions—as are unbalanced translocations. Replication-based mechanisms of rearrangement generate varied chromosomal structures with low-level copy-number gains and frequent inverted rearrangements. One prominent structure consists of 2–7 templates copied from distinct regions of the genome strung together within one locus. Such cycles of templated insertions correlate with tandem duplications, and—in liver cancer—frequently activate the telomerase gene TERT. A wide variety of rearrangement processes are active in cancer, which generate complex configurations of the genome upon which selection can act.
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| 8. |
- Alqedra, Mohammed K., et al.
(författare)
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Optical coherence properties of Kramers' rare-earth ions at the nanoscale for quantum applications
- 2023
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Ingår i: Physical Review B. - 2469-9950. ; 108:7
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Tidskriftsartikel (refereegranskat)abstract
- Rare Earth (RE) ion doped nanomaterials are promising candidates for a range of quantum technology applications. Among RE ions, the so-called Kramers' ions possess spin transitions in the GHz range at low magnetic fields, which allows for high-bandwidth multimode quantum storage, fast qubit operations as well as interfacing with superconducting circuits. They also present relevant optical transitions in the infrared. In particular, Er3+ has an optical transition in the telecom band, while Nd3+ presents a high-emission-rate transition close to 890 nm. In this paper, we measure spectroscopic properties that are of relevance to using these materials in quantum technology applications. We find the inhomogeneous linewidth to be 10.7 GHz for Er3+ and 8.2 GHz for Nd3+, and the excited state lifetime T1 to be 13.68 ms for Er3+ and 540μs for Nd3+. We study the dependence of homogeneous linewidth on temperature for both samples, with the narrowest linewidth being 379 kHz (T2=839 ns) for Er3+ measured at 3 K, and 62 kHz (T2=5.14μs) for Nd3+ measured at 1.6 K. Further, we investigate time-dependent homogeneous linewidth broadening due to spectral diffusion and the dependence of the homogeneous linewidth on magnetic field to get additional clarity of mechanisms that can influence the coherence time. In light of our results, we discuss two applications: single qubit-state readout and a Fourier-limited single photon source.
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| 9. |
- Bengtsson, S., et al.
(författare)
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Space–time control of free induction decay in the extreme ultraviolet
- 2017
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 11:4, s. 252-258
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Tidskriftsartikel (refereegranskat)abstract
- Ultrafast extreme-ultraviolet (XUV) and X-ray sources are revolutionizing our ability to follow femtosecond processes with ångström-scale resolution. The next frontier is to simultaneously control the direction, duration and timing of such radiation. Here, we demonstrate a fully functional opto-optical modulator for XUV light, similar to modulators available at infrared (IR) and visible wavelengths. It works by using an IR pulse to control the spatial and spectral phase of the free induction decay that results from using attosecond pulses to excite a gas. The modulator allows us to send the XUV light in a direction of our choosing at a time of our choosing. The inherent synchronization of the XUV emission to the control pulse will allow laser-pump/X-ray probe experiments with sub-femtosecond time resolution.
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| 10. |
- Horvath, Sebastian P., et al.
(författare)
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Noise-free on-demand atomic frequency comb quantum memory
- 2021
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Ingår i: Physical Review Research. - 2643-1564. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- We present an extension of the atomic frequency comb protocol that utilizes the Stark effect to perform noise-free, on-demand, control. An experimental realization of this protocol was implemented in the Pr3+:Y2SiO5 solid-state system, and a recall efficiency of 38% for a 0.8 μs storage time was achieved. Experiments were performed with both bright pulses as well as weak-coherent states, the latter achieving a signal-to-noise ratio of 570±120 using input pulses with an average photon number of ∼0.1. The principal limitation for a longer storage time was found to be the minimum peak width attainable for Pr3+:Y2SiO5. We employ an adaptation of an established atomic frequency comb model to investigate an on-demand, wide-bandwidth, memory based on Eu3+:Y2SiO5. From this, we determine that a storage time as long as 100 μs may be practical even without recourse to spin-wave storage.
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