ArticleJournal of cancer research and clinical oncology2023
Identification of rs2736099 as a novel cis-regulatory variation for TERT and implications for tumorigenesis and cell proliferation.
Article in Journal of cancer research and clinical oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma.Nature communications · 2026Article
- The era of prostate-specific membrane antigen (PSMA)-based theranostics for hepatocellular carcinoma is upcoming: are we ready for it?European journal of nuclear medicine and molecular imaging · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
purposeLung cancer is a malignant tumor with obvious genetic predisposition. Association studies have proposed that rs2853677, a SNP localizing at intron region of TERT (telomerase reverse transcriptase), is significantly associated with TERT expression, telomere length and eventually lung cancer risk. However, functional genomics work indicates that rs2853677 is not with the ability to alter gene expression. All these facts make us hypothesize that some other genetic variation(s) are in linkage disequilibrium (LD) with rs2853677 and influence TERT expression.
methodsLD pattern in rs2853677 nearby region was analyzed based on 1000 genomes data for three representative populations in the world and functional genomics research was performed for this locus.
resultsOnly one SNP, rs2736099, is in strong LD with rs2853677 in East Asian. Dual-luciferase reporter assay verifies that rs2736099 can regulate gene expression and should be the causal SNP for this disease. Through chromosome conformation capture assay, it is disclosed that the enhancer surrounding rs2736099 can interact with TERT promoter. Through chromatin immunoprecipitation, the transcription factor SP1 (Sp1 transcription factor) is recognized for the chromatin segment spanning rs2736099.
conclusionsOur results provide the missing piece between genetic variation at this locus and lung cancer risk, which is also applied to tumorigenesis in other tissues and cell proliferation.
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