| 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. |
- Valenti, S., et al.
(author)
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PESSTO spectroscopic classification of La Silla-Quest Transients
- 2012
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Reports (other academic/artistic)abstract
- PESSTO is the "Public ESO Spectroscopic Survey of Transient Objects" (http://www.pessto.org) using the ESO New Technology Telescope (NTT) at La Silla and the EFOSC2 (optical) and SOFI (near-IR) spectrographs. It is one of two currently running public spectroscopic surveys at ESO. The survey details are as follows: - PESSTO has 90 nights per year on the NTT: 9 lunations (August to April), 10 nights per lunation (we are not observing May-July).
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| 3. |
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| 4. |
- Brennan, S. J., et al.
(author)
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Photometric and spectroscopic evolution of the interacting transient AT 2016jbu(Gaia16cfr)
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5642-5665
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Journal article (peer-reviewed)abstract
- We present the results from a high-cadence, multiwavelength observation campaign of AT 2016jbu (aka Gaia16cfr), an interacting transient. This data set complements the current literature by adding higher cadence as well as extended coverage of the light-curve evolution and late-time spectroscopic evolution. Photometric coverage reveals that AT 2016jbu underwent significant photometric variability followed by two luminous events, the latter of which reached an absolute magnitude of MV ∼ −18.5 mag. This is similar to the transient SN 2009ip whose nature is still debated. Spectra are dominated by narrow emission lines and show a blue continuum during the peak of the second event. AT 2016jbu shows signatures of a complex, non-homogeneous circumstellar material (CSM). We see slowly evolving asymmetric hydrogen line profiles, with velocities of 500 km s−1 seen in narrow emission features from a slow-moving CSM, and up to 10 000 km s−1 seen in broad absorption from some high-velocity material. Late-time spectra (∼+1 yr) show a lack of forbidden emission lines expected from a core-collapse supernova and are dominated by strong emission from H, He I, and Ca II. Strong asymmetric emission features, a bumpy light curve, and continually evolving spectra suggest an inhibit nebular phase. We compare the evolution of H α among SN 2009ip-like transients and find possible evidence for orientation angle effects. The light-curve evolution of AT 2016jbu suggests similar, but not identical, circumstellar environments to other SN 2009ip-like transients.
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| 5. |
- Brennan, S. J., et al.
(author)
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Progenitor, environment, and modelling of the interacting transient AT 2016jbu (Gaia16cfr)
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 513:4, s. 5666-5685
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Journal article (peer-reviewed)abstract
- We present the bolometric light curve, identification and analysis of the progenitor candidate, and preliminary modelling of AT 2016jbu (Gaia16cfr). We find a progenitor consistent with a ∼ 22–25 M⊙ yellow hypergiant surrounded by a dusty circumstellar shell, in agreement with what has been previously reported. We see evidence for significant photometric variability in the progenitor, as well as strong Hα emission consistent with pre-existing circumstellar material. The age of the environment, as well as the resolved stellar population surrounding AT 2016jbu, supports a progenitor age of >10 Myr, consistent with a progenitor mass of ∼22 M⊙. A joint analysis of the velocity evolution of AT 2016jbu and the photospheric radius inferred from the bolometric light curve shows the transient is consistent with two successive outbursts/explosions. The first outburst ejected material with velocity ∼650 km s−1, while the second, more energetic event ejected material at ∼4500 km s−1. Whether the latter is the core collapse of the progenitor remains uncertain. We place a limit on the ejected 56Ni mass of <0.016 M⊙. Using the Binary Population And Spectral Synthesis (BPASS) code, we explore a wide range of possible progenitor systems and find that the majority of these are in binaries, some of which are undergoing mass transfer or common-envelope evolution immediately prior to explosion. Finally, we use the SuperNova Explosion Code (SNEC) to demonstrate that the low-energy explosions within some of these binary systems, together with sufficient circumstellar material, can reproduce the overall morphology of the light curve of AT 2016jbu.
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| 6. |
- Mourikis, TP, et al.
(author)
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3101-
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Journal article (peer-reviewed)abstract
- The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
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| 9. |
- Turkington, RC, et al.
(author)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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In: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Journal article (peer-reviewed)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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