High levels of global genome methylation in patients with retinoblastoma

Yazıcı, Hülya; Wu, Hui-Chen; Tığlı, Hülya; Yılmaz, Elif Zeynep; Kebudi, Rejin; Santella, Regina M.

High levels of global genome methylation in patients with retinoblastoma

dc.contributor.author	Yazıcı, Hülya
dc.contributor.author	Wu, Hui-Chen
dc.contributor.author	Tığlı, Hülya
dc.contributor.author	Yılmaz, Elif Zeynep
dc.contributor.author	Kebudi, Rejin
dc.contributor.author	Santella, Regina M.
dc.date.accessioned	2020-07-27T07:13:30Z
dc.date.available	2020-07-27T07:13:30Z
dc.date.issued	2020
dc.department	İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.description.abstract	Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (DNMT1) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (RB1). Thus, there is a direct interaction betweenDNMT1andRB1 in vivo. The present study hypothesized that uncontrolledDNMT1, DNMT2andDNMT3expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, inRB1and/or inactivation of other genes in retinal cells. To test this, the global genome methylation levels were analyzed in 69 patients with retinoblastoma, as well as 26 healthy siblings and 18 healthy unrelated children as the control groups. Peripheral blood and tumor tissue samples were obtained from 32 patients. The expression levels ofDNMTgenes were also determined in cell lines. Based on the median levels of global genome methylation in patients, higher genome-wide methylation levels in peripheral blood were associated with a 3.33-fold increased risk for retinoblastoma in patients compared with all healthy controls (95% confidence interval, 0.98-11.35; P<0.0001). The level of global genome methylation and the expression ofDNMTgenes were increased in the WERI-RB-1 cell line, which has a mutatedRB1gene, compared with a wild-typeRB1-expressing cell line. These results supported the hypothesis that epigenetic alterations, as well as mutations inRB1, may be associated with the oncogenesis and inheritance of retinoblastoma. The repression of genes that interact withRB1, such as theDNMTgene family, may be important in patients with retinoblastoma with alterations inRB1, and may serve a role in the treatment and regression of retinoblastoma.
dc.description.sponsorship	Istanbul University Istanbul University-Cerrahpasa AVON-AACR foundation	en_US
dc.identifier.citation	Yazıcı, H., Wu, Hui-C., Tığlı, H., Yılmaz, E. Z., Kebudi, R. ve Santella, R. M. (2020). High levels of global genome methylation in patients with retinoblastoma. Oncology Letters, 20(1), 715-723. https://dx.doi.org/10.3892/ol.2020.11613
dc.identifier.doi	10.3892/ol.2020.11613
dc.identifier.endpage	723
dc.identifier.issn	1792-1074
dc.identifier.issn	1792-1082
dc.identifier.issue	1
dc.identifier.scopusquality	Q3
dc.identifier.startpage	715
dc.identifier.uri	https://dx.doi.org/10.3892/ol.2020.11613
dc.identifier.uri	https://hdl.handle.net/20.500.12511/5606
dc.identifier.volume	20
dc.identifier.wosquality	Q4
dc.indekslendigikaynak	Web of Science
dc.indekslendigikaynak	Scopus
dc.indekslendigikaynak	PubMed
dc.language.iso	en
dc.publisher	Spandidos Publications
dc.relation.ispartof	Oncology Letters	en_US
dc.relation.publicationcategory	Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rights	Attribution-NonCommercial-NoDerivatives 4.0 International	*
dc.rights	info:eu-repo/semantics/openAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/	*
dc.subject	Global Genome Methylation
dc.subject	DNA Methyltransferase Genes
dc.subject	Gene Expression
dc.subject	Retinoblastoma
dc.title	High levels of global genome methylation in patients with retinoblastoma
dc.type	Article