| 1. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 2. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 3. |
- Mikkelsen, Tarjei, et al.
(författare)
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Initial sequence of the chimpanzee genome and comparison with the human genome
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 437:7055, s. 69-87
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a draft genome sequence of the common chimpanzee (Pan troglodytes). Through comparison with the human genome, we have generated a largely complete catalogue of the genetic differences that have accumulated since the human and chimpanzee species diverged from our common ancestor, constituting approximately thirty-five million single-nucleotide changes, five million insertion/deletion events, and various chromosomal rearrangements. We use this catalogue to explore the magnitude and regional variation of mutational forces shaping these two genomes, and the strength of positive and negative selection acting on their genes. In particular, we find that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles. We also use the chimpanzee genome as an outgroup to investigate human population genetics and identify signatures of selective sweeps in recent human evolution.
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| 4. |
- Bailey, Matthew H., et al.
(författare)
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Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
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| 5. |
- Osmont, Dimitri, et al.
(författare)
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An 800-year high-resolution black carbon ice core record from Lomonosovfonna, Svalbard
- 2018
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Ingår i: Atmospheric Chemistry And Physics. - : COPERNICUS GESELLSCHAFT MBH. - 1680-7316 .- 1680-7324. ; 18:17, s. 12777-12795
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Tidskriftsartikel (refereegranskat)abstract
- Produced by the incomplete combustion of fossil fuel and biomass, black carbon (BC) contributes to Arctic warming by reducing snow albedo and thus triggering a snow-albedo feedback leading to increased snowmelt. Therefore, it is of high importance to assess past BC emissions to better understand and constrain their role. However, only a few long-term BC records are available from the Arctic, mainly originating from Greenland ice cores. Here, we present the first long-term and high-resolution refractory black carbon (rBC) record from Svalbard, derived from the analysis of two ice cores drilled at the Lomonosovfonna ice field in 2009 (LF-09) and 2011 (LF-11) and covering 800 years of atmospheric emissions. Our results show that rBC concentrations strongly increased from 1860 on due to anthropogenic emissions and reached two maxima, at the end of the 19th century and in the middle of the 20th century. No increase in rBC concentrations during the last decades was observed, which is corroborated by atmospheric measurements elsewhere in the Arctic but contradicts a previous study from another ice core from Svalbard. While melting may affect BC concentrations during periods of high temperatures, rBC concentrations remain well preserved prior to the 20th century due to lower temperatures inducing little melt. Therefore, the preindustrial rBC record (before 1800), along with ammonium (NH4+), formate (HCOO-) and specific organic markers (vanillic acid, VA, and p-hydroxybenzoic acid, p-HBA), was used as a proxy for biomass burning. Despite numerous single events, no long-term trend was observed over the time period 1222-1800 for rBC and NH4+. In contrast, formate, VA, and p-HBA experience multi-decadal peaks reflecting periods of enhanced biomass burning. Most of the background variations and single peak events are corroborated by other ice core records from Greenland and Siberia. We suggest that the paleofire record from the LF ice core primarily reflects biomass burning episodes from northern Eurasia, induced by decadal-scale climatic variations.
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