ArticleGenome research2012
Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus.
Article in Genome research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 5 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 5 syntheses or guidelines pooled it, 121 citations in OpenAlex.
- Germline Genetic Variants Associated with Somatic TMPRSS2:ERG Fusion Status in Prostate Cancer: A Genome-Wide Association Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- A multiethnic meta-analysis defined the association of rs12946942 with severe adolescent idiopathic scoliosis.Journal of human genetics · 2019Pooled it
- Gene regulatory mechanisms underpinning prostate cancer susceptibility.Nature genetics · 2016Pooled it
- Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.Nature · 2015Pooled it
- Multi-omics dissection of FOXA1 reveals cancer-type-specific transcriptional networks and functional risk variants.iScience · 2026Article
- Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.Endocrine-related cancer · 2026Review
- Upstream SOX9 deletion in a 46,XY girl with acampomelic campomelic dysplasia and absent minipuberty.Orphanet journal of rare diseases · 2025Article
- The Germline and Somatic Origins of Prostate Cancer Heterogeneity.Cancer discovery · 2025Article
- Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.Nature communications · 2025Article
- Rapid and Quantitative Functional Interrogation of Human Enhancer Variant Activity in Live Mice.bioRxiv : the preprint server for biology · 2023Article
- Transposable Elements Are Co-opted as Oncogenic Regulatory Elements by Lineage-Specific Transcription Factors in Prostate Cancer.Cancer discovery · 2023Article
- Article
- Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture.Cancer discovery · 2022Article
- Review
- An enhancer variant at 16q22.1 predisposes to hepatocellular carcinoma via regulating PRMT7 expression.Nature communications · 2022Article
- Germline RAD51B variants confer susceptibility to breast and ovarian cancers deficient in homologous recombination.NPJ breast cancer · 2021Article
- TCGA database analysis of the tumor mutation burden and its clinical significance in colon cancer.Journal of gastrointestinal oncology · 2021Article
- Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence.Nature genetics · 2021Article
- CRISPRi screens reveal a DNA methylation-mediated 3D genome dependent causal mechanism in prostate cancer.Nature communications · 2021Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWAS) are identifying genetic predisposition to various diseases. The 17q24.3 locus harbors the single nucleotide polymorphism (SNP) rs1859962 that is statistically associated with prostate cancer (PCa). It defines a 130-kb linkage disequilibrium (LD) block that lies in an ∼2-Mb gene desert area. The functional biology driving the risk associated with this LD block is unknown. Here, we integrate genome-wide chromatin landscape data sets, namely, epigenomes and chromatin openness from diverse cell types. This identifies a PCa-specific enhancer within the rs1859962 risk LD block that establishes a 1-Mb chromatin loop with the SOX9 gene. The rs8072254 and rs1859961 SNPs mapping to this enhancer impose allele-specific gene expression. The variant allele of rs8072254 facilitates androgen receptor (AR) binding driving increased enhancer activity. The variant allele of rs1859961 decreases FOXA1 binding while increasing AP-1 binding. The latter is key to imposing allele-specific gene expression. The rs8072254 variant in strong LD with the rs1859962 risk SNP can account for the risk associated with this locus, while rs1859961 is a rare variant less likely to contribute to the risk associated with this LD block. Together, our results demonstrate that multiple genetic variants mapping to a unique enhancer looping to the SOX9 oncogene can account for the risk associated with the PCa 17q24.3 locus. Allele-specific recruitment of the transcription factors androgen receptor (AR) and activating protein-1 (AP-1) account for the increased enhancer activity ascribed to this PCa-risk LD block. This further supports the notion that an integrative genomics approach can identify the functional biology disrupted by genetic risk variants.
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Registered trials
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.