| 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. |
- Damineli, Augusto, et al.
(författare)
-
The Long-term Spectral Changes of Eta Carinae : Are they Caused by a Dissipating Occulter as Indicated by CMFGEN Models?
- 2023
-
Ingår i: Astrophysical Journal. - : Institute of Physics Publishing (IOPP). - 0004-637X .- 1538-4357. ; 954
-
Tidskriftsartikel (refereegranskat)abstract
- Eta Carinae (η Car) exhibits a unique set of P Cygni profiles with both broad and narrow components. Over many decades, the spectrum has changed-there has been an increase in observed continuum fluxes and a decrease in Fe II and H I emission-line equivalent widths. The spectrum is evolving toward that of a P Cygni star such as P Cygni itself and HDE 316285. The spectral evolution has been attributed to intrinsic variations such as a decrease in the mass-loss rate of the primary star or differential evolution in a latitudinal-dependent stellar wind. However, intrinsic wind changes conflict with three observational results: the steady long-term bolometric luminosity; the repeating X-ray light curve over the binary period; and the constancy of the dust-scattered spectrum from the Homunculus. We extend previous work that showed a secular strengthening of P Cygni absorptions by adding more orbital cycles to overcome temporary instabilities and by examining more atomic transitions. CMFGEN modeling of the primary wind shows that a time-decreasing mass-loss rate is not the best explanation for the observations. However, models with a small dissipating absorber in our line of sight can explain both the increase in brightness and changes in the emission and P Cygni absorption profiles. If the spectral evolution is caused by the dissipating circumstellar medium, and not by intrinsic changes in the binary, the dynamical timescale to recover from the Great Eruption is much less than a century, different from previous suggestions.
|
|
| 3. |
- Pickett, Connor S., et al.
(författare)
-
Changes in the Na D-1 Absorption Components of eta Carinae Provide Clues on the Location of the Dissipating Central Occulter
- 2022
-
Ingår i: Astrophysical Journal. - : Institute of Physics (IOP). - 0004-637X .- 1538-4357. ; 937:2
-
Tidskriftsartikel (refereegranskat)abstract
- The Na D absorption doublet in the spectrum of eta Carinae is complex, with multiple absorption features associated with the Great Eruption (1840s), the Lesser Eruption (1890s), and the interstellar clouds. The velocity profile is further complicated by the P Cygni profile originating in the system's stellar winds and blending with the He i lambda 5876 profile. The Na D profile contains a multitude of absorption components, including those at velocities of -145 km s(-1), -168 km s(-1), and +87 km s(-1), which we concentrate on in this analysis. Ground-based spectra recorded from 2008 to 2021 show significant variability of the -145 km s(-1) absorption throughout long-term observations. In the high-ionization phases of eta Carinae prior to the 2020 periastron passage, this feature disappeared completely but briefly reappeared across the 2020 periastron, along with a second absorption at -168 km s(-1). Over the past few decades, eta Carinae has been gradually brightening, which is shown to be caused by a dissipating occulter. The decreasing absorption of the -145 km s(-1) component, coupled with similar trends seen in absorptions of ultraviolet resonant lines, indicate that this central occulter was possibly a large clump associated with the Little Homunculus or another clump between the Little Homunculus and the star. We also report on a foreground absorption component at +87 km s(-1). Comparison of Na D absorption in the spectra of nearby systems demonstrates that this redshifted component likely originates in an extended foreground structure consistent with a previous ultraviolet spectral survey in the Carina Nebula.
|
|
