ArticlePLoS genetics2017
Recurrent promoter mutations in melanoma are defined by an extended context-specific mutational signature.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 82 citations in OpenAlex.
- High-throughput characterization of transcription factors that modulate UV damage formation and repair at single-nucleotide resolution.Nature communications · 2026Article
- High-throughput characterization of transcription factors that modulate UV damage formation and repair at single-nucleotide resolution.Research square · 2025Article
- Methods and applications of genome-wide profiling of DNA damage and rare mutations.Nature reviews. Genetics · 2024Review
- Mechanistic basis of atypical TERT promoter mutations.Nature communications · 2024Article
- Melanoma-specific mutation hotspots in distal, non-coding, promoter-interacting regions implicate novel candidate driver genes.British journal of cancer · 2024Article
- Hotspot propensity across mutational processes.Molecular systems biology · 2024Article
- Functional analysis of recurrent CDC20 promoter variants in human melanoma.Communications biology · 2023Article
- Sequence dependencies and mutation rates of localized mutational processes in cancer.Genome medicine · 2023Article
- Structural underpinnings of mutation rate variations in the human genome.Nucleic acids research · 2023Article
- Detecting recurrent passenger mutations in melanoma by targeted UV damage sequencing.Nature communications · 2023Article
- Base-resolution UV footprinting by sequencing reveals distinctive damage signatures for DNA-binding proteins.Nature communications · 2023Article
- Genome-wide maps of rare and atypical UV photoproducts reveal distinct patterns of damage formation and mutagenesis in yeast chromatin.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma.The Journal of pathology · 2023Article
- Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer.Nature communications · 2022Article
- TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma.Science (New York, N.Y.) · 2022Article
- Pan-cancer analysis of mutations in open chromatin regions and their possible association with cancer pathogenesis.Cancer medicine · 2022Article
- Cyclobutane Pyrimidine Dimer Hyperhotspots as Sensitive Indicators of Keratinocyte UV ExposurePhotochemistry and photobiology · 2022Article
- A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues.Scientific reports · 2022Article
- Retinoblastoma protein regulates carcinogen susceptibility at heterochromatic cancer driver loci.Life science alliance · 2022Article
- Mutations in NoncodingMolecular cancer research : MCR · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sequencing of whole tumor genomes holds the promise of revealing functional somatic regulatory mutations, such as those described in the TERT promoter. Recurrent promoter mutations have been identified in many additional genes and appear to be particularly common in melanoma, but convincing functional data such as influence on gene expression has been more elusive. Here, we show that frequently recurring promoter mutations in melanoma occur almost exclusively at cytosines flanked by a distinct sequence signature, TTCCG, with TERT as a notable exception. In active, but not inactive, promoters, mutation frequencies for cytosines at the 5' end of this ETS-like motif were considerably higher than expected based on a UV trinucleotide mutational signature. Additional analyses solidify this pattern as an extended context-specific mutational signature that mediates an exceptional position-specific vulnerability to UV mutagenesis, arguing against positive selection. We further use ultra-sensitive amplicon sequencing to demonstrate that cell cultures exposed to UV light quickly develop subclonal mutations specifically in affected positions. Our findings have implications for the interpretation of somatic mutations in regulatory regions, and underscore the importance of genomic context and extended sequence patterns to accurately describe mutational signatures in cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.