dc.contributor.author | Yazıcı, Hülya | |
dc.contributor.author | Wu, Hui-Chen | |
dc.contributor.author | Tığlı, Hülya | |
dc.contributor.author | Yılmaz, Elif Z. | |
dc.contributor.author | Kebudi, Rejin | |
dc.contributor.author | Santella, Regina M. | |
dc.date.accessioned | 2020-08-08T22:03:01Z | |
dc.date.available | 2020-08-08T22:03:01Z | |
dc.date.issued | 2020 | en_US |
dc.identifier.issn | 1792-1074 | |
dc.identifier.issn | 1792-1082 | |
dc.identifier.uri | https://hdl.handle.net/11363/2345 | |
dc.description | Document Information
Language:English
Accession Number: WOS:000546013100075
PubMed ID: 32565997 | en_US |
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. | en_US |
dc.description.sponsorship | This study was funded by Istanbul University with project number BAY:TAS-2017-23070, Istanbul University-Cerrahpasa with project number BYP-2019-32977 and the AVON-AACR foundation with grant number 2005-2007. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | SPANDIDOS PUBL LTD, POB 18179, ATHENS, 116 10, GREECE | en_US |
dc.relation.isversionof | 10.3892/ol.2020.11613 | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
dc.rights | info:eu-repo/semantics/embargoedAccess | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
dc.subject | global genome methylation | en_US |
dc.subject | DNA methyltransferase genes | en_US |
dc.subject | gene expression | en_US |
dc.subject | retinoblastoma | en_US |
dc.subject | DNA-METHYLTRANSFERASE ACTIVITY | en_US |
dc.subject | G(1) CONTROL | en_US |
dc.subject | CPG ISLANDS | en_US |
dc.subject | EXPRESSION | en_US |
dc.subject | GENE | en_US |
dc.subject | CANCER | en_US |
dc.subject | PROMOTER | en_US |
dc.subject | HYPERMETHYLATION | en_US |
dc.subject | EPIGENETICS | en_US |
dc.subject | PROGRESSION | en_US |
dc.title | High levels of global genome methylation in patients with retinoblastoma | en_US |
dc.type | article | en_US |
dc.relation.ispartof | ONCOLOGY LETTERS | en_US |
dc.department | Sağlık Bilimleri Yüksekokulu | en_US |
dc.identifier.volume | 20 | en_US |
dc.identifier.issue | 1 | en_US |
dc.identifier.startpage | 715 | en_US |
dc.identifier.endpage | 723 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |