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

Weigel, Christoph ; Chaisaingmongkol, Jittiporn ; Assenov, Yassen ; Kuhmann, Christine ; Winkler, Volker ; Santi, Irene ; Bogatyrova, Olga ; Kaucher, Simone ; Bermejo, Justo L. ; Leung, Suet Y. ; Chan, Tsun L. ; Lasitschka, Felix ; Bohrer, Manfred H. ; Marx, Alexander ; Heyny-von Haußen, Roland ; Herold-Mende, Christel ; Dyckhoff, Gerhard ; Boukamp, Petra ; Delank, Klaus W. ; Hörmann, Karl ; Lippert, Burkhard M. ; Baier, Gerald ; Dietz, Andreas ; Oakes, Christopher C. ; Plass, Christoph ; Becher, Heiko ; Schmezer, Peter ; Ramroth, Heribert ; Popanda, Odilia

In: Clinical epigenetics, 11 (2019), Nr. 67. pp. 1-15. ISSN 1868-7083

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Download (1MB) | Lizenz: Creative Commons LizenzvertragDNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer by Weigel, Christoph ; Chaisaingmongkol, Jittiporn ; Assenov, Yassen ; Kuhmann, Christine ; Winkler, Volker ; Santi, Irene ; Bogatyrova, Olga ; Kaucher, Simone ; Bermejo, Justo L. ; Leung, Suet Y. ; Chan, Tsun L. ; Lasitschka, Felix ; Bohrer, Manfred H. ; Marx, Alexander ; Heyny-von Haußen, Roland ; Herold-Mende, Christel ; Dyckhoff, Gerhard ; Boukamp, Petra ; Delank, Klaus W. ; Hörmann, Karl ; Lippert, Burkhard M. ; Baier, Gerald ; Dietz, Andreas ; Oakes, Christopher C. ; Plass, Christoph ; Becher, Heiko ; Schmezer, Peter ; Ramroth, Heribert ; Popanda, Odilia underlies the terms of Creative Commons Attribution 4.0

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Abstract

Background: 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.

Item Type: Article
Journal or Publication Title: Clinical epigenetics
Volume: 11
Number: 67
Publisher: Springer
Place of Publication: Berlin ; Heidelberg
Date Deposited: 27 Jun 2019 09:41
Date: 2019
ISSN: 1868-7083
Page Range: pp. 1-15
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Medizinische Fakultät Heidelberg > Chirurgische Universitätsklinik
Medizinische Fakultät Heidelberg > Institut für Medizinische Biometrie und Informatik
Medizinische Fakultät Heidelberg > Pathologisches Institut
Medizinische Fakultät Heidelberg > Institut für Public Health (IPH)
Subjects: 610 Medical sciences Medicine
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