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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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| 4. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 6. |
- Zaidi, Syed H., et al.
(författare)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 8. |
- Olierook, Hugo K.H., et al.
(författare)
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Bunbury Basalt : Gondwana breakup products or earliest vestiges of the Kerguelen mantle plume?
- 2016
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Ingår i: Earth and Planetary Science Letters. - 0012-821X .- 1385-013X. ; 440, s. 20-32
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Tidskriftsartikel (refereegranskat)abstract
- In this contribution, we investigate the role of a mantle plume in the genesis of the Bunbury Basalt using high-precision 40Ar/39Ar geochronology and whole-rock geochemistry, and by using crustal basement thickness of the eastern Indian Ocean and the western Australian continent. The Bunbury Basalt is a series of lava flows and deep intrusive rocks in southwestern Australia thought to be the earliest igneous products from the proto-Kerguelen mantle plume. Nine new plateau ages indicate that the Bunbury Basalt erupted in three distinct phases, at 136.96±0.43 Ma, 132.71±0.43 Ma and 130.45±0.82 Ma. All Bunbury Basalt samples are enriched tholeiitic basalts with varying contributions from the continental lithosphere that are similar to other Kerguelen plume-products. Based on plate reconstructions and the present geochronological constraints, the eruption of the oldest Bunbury Basalt preceded the emplacement of the Kerguelen large igneous province by at least 10–20 m.y. Such age differences between a precursor and the main magmatic event are not uncommon but do require additional explanation. Low crustal stretching factors beneath the Bunbury Basalt (β≈1.4) indicate that decompression melting could not have been generated from asthenospheric mantle with a normal chemistry and geotherm. An elevated geotherm from the mantle plume coupled with the geochemical similarity between the Bunbury Basalt and other Kerguelen plume-products suggests a shared origin exists. However, new age constraints of the oldest Bunbury Basalt are synchronous with the breakup of eastern Gondwana and the initial opening of the Indian Ocean at ca. 137–136 Ma, which may mean an alternative explanation is possible. The enriched geochemistry can equally be explained by a patch of shallow mantle beneath the southern Perth Basin. The patch may have been enriched during Gondwana suturing at ca. 550–500 Ma, during early rifting events by magmatic underplating or by intruded melts into the subcontinental lithospheric mantle. This enriched geochemical signature would then be sufficient to trigger decompression melting from passive rifting between Greater India and Australia with no contribution from the Kerguelen hotspot. We conclude that although the proto-Kerguelen hotspot is certainly a possible explanation for the genesis of the Bunbury Basalt, decompression melting of an enriched patch of subcontinental lithospheric mantle is an alternative theory.
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| 9. |
- Ozolins, D., et al.
(författare)
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Second European multi-disciplinary conference of national strategies for Chlamydia trach. and human papillomavirus NSCP conf. in Berlin, 2013 enhanced detection, management and surveillance of sexually transmitted infections in Europe are essential!
- 2013
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Ingår i: International journal of immunopathology and pharmacology. - : SAGE Publications. - 0394-6320 .- 2058-7384. ; 26:4, s. 839-845
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for updated guidance on detection, management and surveillance of sexually transmitted infections (STIs). Chlamydia, gonorrhoea and syphilis reporting needs to be mandatory in more European countries to aid collection of data. More widespread Chlamydia screening is needed in many countries as this is the only way to reduce complications. The role of Human Papillomavirus (HPV) screening in a situation where the prevalence of HPV infection has dropped significantly was also discussed in the context of the high cost of screening, the need for a relatively complex infrastructure, particularly in developing countries, and falling vaccination costs. An integrated HPV vaccination and screening policy could be the most appropriate with vaccination at 9-13 years as recommended by WHO and a single HPV screen at 35-39 years, possibly repeated thereafter every 10 years. Female and male HPV vaccination programmes could lead to near elimination of genital warts in both females and males. Surveillance of STIs should be intensified where needed; additional or better quality data should be collected including reasons for testing, denominator data to estimate positivity rates, diagnostic methods, concurrent STIs, sexual orientation and country of acquisition; more analytical rather than descriptive epidemiology is needed.
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| 10. |
- Quintero, Raiza R., et al.
(författare)
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Shocked quartz in sandstone from the buried Ilkurlka impact structure, Officer Basin, Western Australia
- 2024
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Ingår i: Meteoritics and Planetary Science. - 1086-9379. ; 59:1, s. 68-87
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Tidskriftsartikel (refereegranskat)abstract
- The Ilkurlka structure is an ~12 km diameter buried circular aeromagnetic anomaly within the Officer Basin in Western Australia. Prior studies postulated a range of origins, including meteorite impact. We report the presence of pervasive deformation in the first drill cores from the structure. Brecciated sandstone and siltstone contain arrays of quartz grains with concussion fractures and rare shocked quartz grains with planar deformation features (PDF). Universal stage measurements of two quartz grains reveal one grain with PDF parallel to (0001) orientation and three PDF sets parallel to (Formula presented.). A second grain contains three PDF sets parallel to (Formula presented.) and one set parallel to (Formula presented.). The shocked grains are interpreted to have formed in situ, rather than representing transported detrital shocked grains. These results suggest local shock compression of at least 10 GPa; however, preservation of primary porosity and overall paucity of shocked grains may indicate lower mean shock pressures. (U-Th)/He dating of 58 apatite grains from four samples across both cores shows a dominant age population at ~265 Ma and a minor age population at ~135 Ma. These dates overlap with regional events and thus do not provide an unambiguous impact age. An upper Carboniferous to lower Permian maximum impact age is provisionally proposed based on inferred missing target rock stratigraphy.
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| 11. |
- Spencer, Rebecca, et al.
(författare)
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EVERREST prospective study : A 6-year prospective study to define the clinical and biological characteristics of pregnancies affected by severe early onset fetal growth restriction
- 2017
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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation. Methods: This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death. Discussion: The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR. Trial registration:NCT02097667registered 31st October 2013.
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| 12. |
- Wastegård, Stefan, et al.
(författare)
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Towards a Holocene tephrochronology for the Faroe Islands, North Atlantic
- 2018
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 195, s. 195-214
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Tidskriftsartikel (refereegranskat)abstract
- The Faroe Islands hold a key position in the North Atlantic region for tephra studies due to their relative proximity to Iceland. Several tephras have been described over the last 50 years in peat and lake sediment sequences, including the type sites for the Saksunarvatn and Mjauvotn tephras. Here we present a comprehensive overview of Holocene tephras found on the Faroe Island. In total 23 tephra layers are described including visible macrotephras such as the Saksunarvatn and Hekla 4 tephras and several cryptotephras. The importance of tephras originally described from the Faroe Islands is highlighted and previously unpublished results are included. In addition, full datasets for several sites are published here for the first time. The Saksunarvatn Ash, now considered to be the result of several eruptions rather than one major eruption, can be separated into two phases on the Faroe Islands; one early phase with two precursor eruptions with lower MgO concentrations (4.5-5.0 wt%) than the main eruption and a later phase with higher MgO concentrations (5.5-6.0 wt%), including the visible Saksunarvatn Ash. The Tjornuvik Tephra, previously considered to be a primary deposit, is now interpreted as a reworked tephra with material from at least two middle Holocene eruptions of Hekla. Several of the tephras identified on the Faroe Islands provide useful isochrons for climate events during the Holocene.
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