Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

ABSTRACT: Mutational signatures can reveal properties of underlying mutational processes and are important when assessing signals of selection in cancer. Here we describe the sequence characteristics of mutations induced by ultraviolet (UV) light, a major mutagen in several human cancers, in terms of extended (longer than trinucleotide) patterns as well as variability of the signature across chromatin states. Promoter regions display a distinct UV signature with reduced TCG>TTG transitions, and genome-wide mapping of UVB-induced DNA photoproducts (pyrimidine dimers) showed that this may be explained by decreased damage formation at hypomethylated promoter CpG sites. Further, an extended signature model encompassing additional information from longer contextual patterns improves modeling of UV mutations, which may enhance discrimination between drivers and passenger events. Our study presents a refined picture of the UV signature and underscores that the characteristics of a single mutational process may vary across the genome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE127966 | GEO | 2019/09/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

UVDE-HS-seq mapping of UV-induced 6-4PPs and atypical TA photoproducts

Project description:We used a novel high-throughput sequencing method known as UVDE-HS-seq to map the formation of UV-induced 6-4 photoproducts (6-4PP) and atypical thymidine-adenine (TA) photoproducts at single nucleotide resolution across the yeast genome in wild-type cells. We also analyzed 6-4PP and TA photoproducts in UV-irradiated yeast genomic DNA (i.e., naked DNA).

2023-02-28 | GSE214217 | GEO

Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

Project description:Intragenomic variability and extended sequence patterns in the mutational signature of ultraviolet light

| PRJNA526021 | ENA

UVDE-seq mapping of UV-induced 6-4PPs and atypical TA photoproducts

Project description:We used a novel high-throughput sequencing method known as UVDE-seq to map the formation of UV-induced 6-4 photoproducts (6-4PP) and atypical thymidine-adenine (TA) photoproducts at single nucleotide resolution across the yeast genome in wild-type and rad16 mutant cells, which are deficient in GG-NER. We also analyzed 6-4PP and TA photoproducts in UV-irradiated yeast genomic DNA (i.e., naked DNA).

2023-02-28 | GSE190471 | GEO

Transcriptome analysis identifies the dysregulation of ultraviolet target genes in human skin cancers

Project description:In this study, we performed RNA-Seq studies to generate a transcriptomic cohort containing UV-responsive genes in human skin cells exposed to different UVR conditions. We then performed rigorous bioinformatics analysis to define a UV gene expression signature that is conserved among cells from different donors. We further demonstrated that the UV signature genes are significantly enriched in genes dysregulated in human skin squamous cell carcinomas.

2018-12-01 | GSE85443 | GEO

Genome-wide analysis of human global and transcription-coupled excision repair of UV damage at single-nucleotide resolution

Project description:We developed a method for genome-wide mapping of DNA excision repair named XR-seq (eXcision Repair-seq). Human nucleotide excision repair generates two incisions surrounding the site of damage, creating a ~30-mer. In XR-seq, this fragment is isolated and subjected to high-throughput sequencing. We used XR-seq to produce stranded, nucleotide-resolution maps of repair of two UV-induced DNA damages in human cells, cyclobutane pyrimidine dimers (CPDs) and (6-4) pyrimidine-pyrimidone photoproducts ((6-4)PPs). In wild-type cells, CPD repair was highly associated with transcription, specifically with the template strand. Experiments in cells defective in either transcription-coupled excision repair or general excision repair isolated the contribution of each pathway to the overall repair pattern, and showed that transcription-coupled repair of both photoproducts occurs exclusively on the template strand. XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bi-directional eRNA production at enhancers. XR-seq data also uncovered the repair characteristics and novel sequence preferences of CPDs and (6-4)PPs. XR-seq and the resulting repair maps will facilitate studies of the effects of genomic location, chromatin context, transcription, and replication on DNA repair in human cells. We have performed XR-seq for two types of UV-induced damages (CPD and (6-4)PP) in three different cell lines: NHF1, XP-C (XP4PA-SV-EB, GM15983)), and CS-B (CS1ANps3g2, GM16095). Two biological replicates were performed for each experiment, in which independent cell populations were UV treated and subjected to XR-seq.

2015-04-19 | E-GEOD-67941 | biostudies-arrayexpress

Genomic Sites Ultrasensitive to Ultraviolet Radiation

Project description:If the genome contains outlier sequences extraordinarily sensitive to environmental agents, these would be sentinels for monitoring personal carcinogen exposure and might drive direct changes in cell physiology rather than acting through rare mutations. New methods, adductSeq and freqSeq, provided statistical resolution to quantify rare lesions at single-base resolution across the genome. Primary human melanocytes, but not fibroblasts, carried spontaneous apurinic sites and TG sequence lesions more frequently than UV-induced cyclobutane pyrimidine dimers (CPDs). UV exposure revealed hyperhotspots acquiring CPDs up to 170 fold more frequently than the genomic average; these sites were more prevalent in melanocytes. Hyperhotspots were disproportionately located near genes, particularly for RNA-binding proteins, with the most-recurrent hyperhotspots at a fixed position within two motifs: one occurring at ETS1 transcription factor binding sites, known to be UV targets, and at sites of mTOR/TOP-tract translation regulation; the second occurring at A2-15TTCTY, which developed "dark CPDs" after UV exposure, repaired CPDs slowly, and had accumulated CPDs prior to the experiment. Motif locations active as hyperhotspots differed between cell types. Melanocyte CPD hyperhotspots aligned precisely with recurrent UV signature mutations in individual gene promoters of melanomas and with known cancer drivers. At sunburn levels of UV exposure, every cell would have a hyperhotspot CPD in each of the ~20 targeted cell pathways, making hyperhotspots act as epigenetic marks. Purpose: These experiments searched for genomic sites in human primary fibroblasts and melanocytes that are extraordinarily sensitive to DNA damage, primarily cyclobutane pyrimidine dimers (CPDs) induced by UVC or UVB radiation. They separately detected abasic sites and other spontaneous DNA damage when present.

2020-04-14 | GSE137226 | GEO

Genome-wide CPD repair maps of Caenorhabditis elegans

Project description:We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single-nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine dimers (CPD) photoproducts in the Caenorhabditis elegans (C. elegans) genome.

2024-04-02 | GSE262486 | GEO

Ultraviolet radiation shapes dendritic cell leukaemia transformation in the skin

Project description:Tumours most often arise from progression of precursor clones within a single anatomical niche. In the bone marrow, clonal progenitors can undergo malignant transformation to acute leukaemia, or differentiate into immune cells that contribute to disease pathology in peripheral tissues. Outside the marrow, these clones are potentially exposed to a variety of tissue-specific mutational processes, although the consequences of this are unclear. Here we investigate the development of blastic plasmacytoid dendritic cell neoplasm (BPDCN)-an unusual form of acute leukaemia that often presents with malignant cells isolated to the skin. Using tumour phylogenomics and single-cell transcriptomics with genotyping, we find that BPDCN arises from clonal (premalignant) haematopoietic precursors in the bone marrow. We observe that BPDCN skin tumours first develop at sun-exposed anatomical sites and are distinguished by clonally expanded mutations induced by ultraviolet (UV) radiation. A reconstruction of tumour phylogenies reveals that UV damage can precede the acquisition of alterations associated with malignant transformation, implicating sun exposure of plasmacytoid dendritic cells or committed precursors during BPDCN pathogenesis. Functionally, we find that loss-of-function mutations in Tet2, the most common premalignant alteration in BPDCN, confer resistance to UV-induced cell death in plasmacytoid, but not conventional, dendritic cells, suggesting a context-dependent tumour-suppressive role for TET2. These findings demonstrate how tissue-specific environmental exposures at distant anatomical sites can shape the evolution of premalignant clones to disseminated cancer.

2023-03-27 | GSE227690 | GEO

Effect of solar ultraviolet radiation on grape berry skin transcriptome

Project description:UV radiation (UV) alters secondary metabolism in the skin of Vitis vinifera L. berries, which may affect on the final composition of both, grapes and wines. We compared berry skin transcriptome and phenolic composition between Tempranillo berries grown in the presence or absence of solar UV in a mid-altitude Tempranillo vineyard. By analysing two different ripening degrees, expression of 121 genes was significantly altered. Functional enrichment identified that, principally, secondary metabolism-related transcripts were induced by UV, including VvFLS1, VvGT5 and VvGT6 flavonol biosynthetic genes induction. Concurrently, flavonol accumulation was the most evident impact of UV on the berry skin phenolic composition. Monoterpenoid biosynthetic transcripts were also up-regulated by UV, whereas induction of stilbenoid biosynthetic transcripts and stilbenes accumulation was probably induced by the joint action of UV and other condition under the UV-blocking filter, likely higher temperature. Among regulatory genes, VvMYBF1, VvMYB24 and three bHLH transcription factors were up-regulated by UV. Homologs to Arabidopsis UVR8-dependent UV-B-induced genes were also induced, including VvHY5-1, VvHY5-2 and VvRUP UV-B signalling genes. This suggests that the UV-B-specific signalling pathway is activated in the skin of grapes grown at low-medium altitudes. The biosynthesis and accumulation of UV-absorbing compounds that are appreciated for winemaking were almost specifically triggered, which indicates that viticultural practices increasing solar UV incidence may improve grape features important to wine production.

2014-09-09 | GSE54636 | GEO

Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.

Project description:Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer. Keywords: time course, ultraviolet irradiation, UV, erbB2, mouse skin

2006-07-01 | GSE4066 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data