ArticleNature genetics2017
Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma.
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
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- Genome-wide methylation profiles of primary and matched distant metastasis: insights from the Dutch Early-Stage melanoma (D-ESMEL) study.Human genomics · 2025Article
- Large-scale multiomic analysis identifies non-coding somatic driver mutations and nominatesGut · 2025Article
- The Noncoding Mutational Landscape of Pancreatic Cancer Reveals Recurrent Somatic Mutations in Enhancer Regions.Cancer research communications · 2025Article
- Novel Therapies in Advanced Pancreatic Cancer: A Peak Beyond the Realms of Gene Targeting.Cureus · 2025Review
- Role of noncoding RNA and protein interaction in pancreatic cancer.Chinese medical journal · 2025Review
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- Cis-regulatory mutations associate with transcriptional and post-transcriptional deregulation of gene regulatory programs in cancers.Nucleic acids research · 2022Article
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- ATP13A3 facilitates polyamine transport in human pancreatic cancer cells.Scientific reports · 2022Article
- Pancreatic cancer evolution and heterogeneity: integrating omics and clinical data.Nature reviews. Cancer · 2022Review
- Functional annotation of noncoding mutations in cancer.Life science alliance · 2021Article
- HOXD13 promotes the malignant progression of colon cancer by upregulating PTPRN2.Cancer medicine · 2021Article
- The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.Signal transduction and targeted therapy · 2021Review
- Drivers of Gene Expression Dysregulation in Pancreatic Cancer.Trends in cancer · 2021Review
- The pancreatic cancer genome revisited.Nature reviews. Gastroenterology & hepatology · 2021Review
- Interpretation of allele-specific chromatin accessibility using cell state-aware deep learning.Genome research · 2021Article
- Solute carrier family 12 member 8 impacts the biological behaviors of breast carcinoma cells by activating TLR/NLR signaling pathway.Cytotechnology · 2021Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
The contributions of coding mutations to tumorigenesis are relatively well known; however, little is known about somatic alterations in noncoding DNA. Here we describe GECCO (Genomic Enrichment Computational Clustering Operation) to analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas (PDAs) and identify commonly mutated regulatory regions. We find recurrent noncoding mutations to be enriched in PDA pathways, including axon guidance and cell adhesion, and newly identified processes, including transcription and homeobox genes. We identified mutations in protein binding sites correlating with differential expression of proximal genes and experimentally validated effects of mutations on expression. We developed an expression modulation score that quantifies the strength of gene regulation imposed by each class of regulatory elements, and found the strongest elements were most frequently mutated, suggesting a selective advantage. Our detailed single-cancer analysis of noncoding alterations identifies regulatory mutations as candidates for diagnostic and prognostic markers, and suggests new mechanisms for tumor evolution.
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