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Article: DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

TitleDNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer
Authors
KeywordsEpigenetics
DNA repair
DNA methylation
TREX2
Pan-cancer studies
Issue Date2019
PublisherBioMed Central Ltd. The Journal's web site is located at http://www.clinicalepigeneticsjournal.com
Citation
Clinical Epigenetics, 2019, v. 11, p. article no. 67 How to Cite?
AbstractBackground: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies.
Persistent Identifierhttp://hdl.handle.net/10722/293875
ISSN
2023 Impact Factor: 4.8
2023 SCImago Journal Rankings: 1.727
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWeigel, C-
dc.contributor.authorChaisaingmongkol, J-
dc.contributor.authorAssenov, Y-
dc.contributor.authorKuhmann, C-
dc.contributor.authorWinkler, V-
dc.contributor.authorSanti, I-
dc.contributor.authorBogatyrova, O-
dc.contributor.authorKaucher, S-
dc.contributor.authorBermejo, J-
dc.contributor.authorLeung, SY-
dc.contributor.authorChan, TL-
dc.contributor.authorLasitschka, F-
dc.contributor.authorBohrer, MH-
dc.contributor.authorMarx, A-
dc.contributor.authorHaußen, RHV-
dc.contributor.authorHerold-Mende, C-
dc.contributor.authorDyckhoff, G-
dc.contributor.authorBoukamp, P-
dc.contributor.authorDelank, KW-
dc.contributor.authorHörmann, K-
dc.contributor.authorLippert, BM-
dc.contributor.authorBaier, G-
dc.contributor.authorDietz, A-
dc.contributor.authorOakes, CC-
dc.contributor.authorPlass, C-
dc.contributor.authorBecher, H-
dc.contributor.authorSchmezer, P-
dc.contributor.authorRamroth, H-
dc.contributor.authorPopanda, O-
dc.date.accessioned2020-11-23T08:23:06Z-
dc.date.available2020-11-23T08:23:06Z-
dc.date.issued2019-
dc.identifier.citationClinical Epigenetics, 2019, v. 11, p. article no. 67-
dc.identifier.issn1868-7075-
dc.identifier.urihttp://hdl.handle.net/10722/293875-
dc.description.abstractBackground: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and < 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p < 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies.-
dc.languageeng-
dc.publisherBioMed Central Ltd. The Journal's web site is located at http://www.clinicalepigeneticsjournal.com-
dc.relation.ispartofClinical Epigenetics-
dc.rightsClinical Epigenetics. Copyright © BioMed Central Ltd.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEpigenetics-
dc.subjectDNA repair-
dc.subjectDNA methylation-
dc.subjectTREX2-
dc.subjectPan-cancer studies-
dc.titleDNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer-
dc.typeArticle-
dc.identifier.emailLeung, SY: suetyi@hku.hk-
dc.identifier.authorityLeung, SY=rp00359-
dc.identifier.authorityChan, TL=rp00418-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13148-019-0666-5-
dc.identifier.pmid31053176-
dc.identifier.pmcidPMC6499986-
dc.identifier.scopuseid_2-s2.0-85065221890-
dc.identifier.hkuros320280-
dc.identifier.volume11-
dc.identifier.spagearticle no. 67-
dc.identifier.epagearticle no. 67-
dc.identifier.isiWOS:000467035400001-
dc.publisher.placeUnited Kingdom-
dc.identifier.issnl1868-7075-

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