DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer
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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; Haußen, Roland Heyny-von; 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: CLIN EPIGENETICS, Vol. 11, No. 1, 03.05.2019, p. 67.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer
AU - Weigel, Christoph
AU - Chaisaingmongkol, Jittiporn
AU - Assenov, Yassen
AU - Kuhmann, Christine
AU - Winkler, Volker
AU - Santi, Irene
AU - Bogatyrova, Olga
AU - Kaucher, Simone
AU - Bermejo, Justo L
AU - Leung, Suet Y
AU - Chan, Tsun L
AU - Lasitschka, Felix
AU - Bohrer, Manfred H
AU - Marx, Alexander
AU - Haußen, Roland Heyny-von
AU - Herold-Mende, Christel
AU - Dyckhoff, Gerhard
AU - Boukamp, Petra
AU - Delank, Klaus W
AU - Hörmann, Karl
AU - Lippert, Burkhard M
AU - Baier, Gerald
AU - Dietz, Andreas
AU - Oakes, Christopher C
AU - Plass, Christoph
AU - Becher, Heiko
AU - Schmezer, Peter
AU - Ramroth, Heribert
AU - Popanda, Odilia
PY - 2019/5/3
Y1 - 2019/5/3
N2 - 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.
AB - 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.
U2 - 10.1186/s13148-019-0666-5
DO - 10.1186/s13148-019-0666-5
M3 - SCORING: Journal article
C2 - 31053176
VL - 11
SP - 67
JO - CLIN EPIGENETICS
JF - CLIN EPIGENETICS
SN - 1868-7075
IS - 1
ER -