The GSDME gene promoter is hypermethylated

Stable Identifier
R-HSA-9710490
Type
Reaction [omitted]
Species
Homo sapiens
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5-Methylation of cytosine residues in DNA is a heritable epigenetic mark that regulates gene expression. DNA methyltransferases (DNA MTase, (DNMTs)) catalyze the transfer of the CH3 group from S‑adenosylmethionine (AdoMet) to DNA (Melanie E & Lacey M 2014; Laisne M et al. 2018). DNMTs associate with EZH2 of the Polycomb Repressive Complex 2 (PRC2) (Vire et al. 2006). Aberrant promoter methylation is considered to be a hallmark of cancer (Ehrlich M et al. 2002; Dong Y et al. 2014; Lam K et al. 2016; Croes L et al. 2018). Epigenetic inactivation of GSDME due to hypermethylation of the GSDME promoter region has been linked to tumorigenesis (Akino K et al. 2007; Kim MS et al. 2008a,b; Croes L et al. 2017, 2018; Ibrahim J et al. 2019). Treatment with the DNA methyltransferase inhibitors such as FDA‑approved decitabine (5‑aza‑2'‑deoxycytidine or DAC) may elevate GSDME expression in certain cancer cells (Akino K et al. 2007; Fujikane T et al. 2009).

Literature References
PubMed ID Title Journal Year
18346456 Methylation of the DFNA5 increases risk of lymph node metastasis in human breast cancer

Kim, MS, Lebron, C, Nagpal, JK, Chae, YK, Chang, X, Huang, Y, Chuang, T, Yamashita, K, Trink, B, Ratovitski, EA, Califano, JA, Sidransky, D

Biochem Biophys Res Commun 2008
28404884 DFNA5 promoter methylation a marker for breast tumorigenesis

Croes, L, de Beeck, KO, Pauwels, P, Vanden Berghe, W, Peeters, M, Fransen, E, Van Camp, G

Oncotarget 2017
18223688 Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma

Kim, MS, Chang, X, Yamashita, K, Nagpal, JK, Baek, JH, Wu, G, Trink, B, Ratovitski, EA, Mori, M, Sidransky, D

Oncogene 2008
30993897 Methylation analysis of Gasdermin E shows great promise as a biomarker for colorectal cancer

Ibrahim, J, Op de Beeck, K, Fransen, E, Croes, L, Beyens, M, Suls, A, Vanden Berghe, W, Peeters, M, Van Camp, G

Cancer Med 2019
Participants
Participates
Catalyst Activity

methyltransferase activity of DNMT1,3A,3B:PRC2:Chromatin [nucleoplasm]

This event is regulated
Disease
Name Identifier Synonyms
melanoma DOID:1909 Naevocarcinoma, melanoma, melanoma, malignant melanoma, morphology (morphologic abnormality), malignant melanoma NOS (morphologic abnormality), malignant melanoma (disorder), malignant melanoma, malignant melanoma, malignant melanoma, malignant melanoma
colon cancer DOID:219
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
breast cancer DOID:1612 malignant tumor of the breast, mammary cancer, malignant neoplasm of breast, mammary tumor, primary breast cancer, breast cancer, Ca breast - NOS, breast tumor
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