High levels of global genome methylation in patients with retinoblastoma
Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 ( ) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 ( ). Thus, there is a direct interaction between and . The present study hypothesized that uncont...
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| Veröffentlicht in: | Oncology letters 2020-07, Vol.20 (1), p.715-723 |
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| creator | Yazici, Hülya Wu, Hui-Chen Tigli, Hulya Yilmaz, Elif Z Kebudi, Rejin Santella, Regina M |
| description | Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (
) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (
). Thus, there is a direct interaction between
and
. The present study hypothesized that uncontrolled
and
expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, in
and/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 of
genes 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 |
| doi_str_mv | 10.3892/ol.2020.11613 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7286142</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A632870965</galeid><sourcerecordid>A632870965</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-112a438fc5d001e8d9b03414d60adf0955b444efcc38c03e74317beea255fa043</originalsourceid><addsrcrecordid>eNptkc9rFTEQxxdRbKk9epWA4G2f-b3JRShFfULBi55DNjvZTckmz82-Sv_75tn67AMzhwyZz3yZzLdp3hK8YUrTjzluKKZ4Q4gk7EVzTjpNW4IVfXnMO37WXJZyi-sRkiglXzdnjAoptO7Om-02jBOKcAexoOzRGHNvIxoh5RnQDOt0H-0ackIhoV3NIK0F_Q7rhBZYQ8p9tGXNs33TvPI2Frh8ui-an18-_7jetjffv367vrppnSBsbQmhljPlnRgwJqAG3WPGCR8ktoPHWoiecw7eOaYcZtBxRroewFIhvMWcXTSfHnV3-36GwdV5FhvNbgmzXe5NtsGcVlKYzJjvTEeVJJxWgfdPAkv-tYeymtu8X1Kd2VBOJNZUi-4fNdoIJiSfq5ibQ3HmSjKqOqylqNTmP1SNAebgcgIf6vtJw4dnDRPYuE4lx_1hw-UUbB9Bt-RSFvDHHxJsDt6bHM3Be_PH-8q_e76WI_3XafYAlMOoRw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2416092957</pqid></control><display><type>article</type><title>High levels of global genome methylation in patients with retinoblastoma</title><source>Spandidos Publications Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Yazici, Hülya ; Wu, Hui-Chen ; Tigli, Hulya ; Yilmaz, Elif Z ; Kebudi, Rejin ; Santella, Regina M</creator><creatorcontrib>Yazici, Hülya ; Wu, Hui-Chen ; Tigli, Hulya ; Yilmaz, Elif Z ; Kebudi, Rejin ; Santella, Regina M</creatorcontrib><description>Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (
) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (
). Thus, there is a direct interaction between
and
. The present study hypothesized that uncontrolled
and
expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, in
and/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 of
genes 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 of
genes were increased in the WERI-RB-1 cell line, which has a mutated
gene, compared with a wild-type
-expressing cell line. These results supported the hypothesis that epigenetic alterations, as well as mutations in
, may be associated with the oncogenesis and inheritance of retinoblastoma. The repression of genes that interact with
, such as the
gene family, may be important in patients with retinoblastoma with alterations in
, and may serve a role in the treatment and regression of retinoblastoma.</description><identifier>ISSN: 1792-1074</identifier><identifier>EISSN: 1792-1082</identifier><identifier>DOI: 10.3892/ol.2020.11613</identifier><identifier>PMID: 32565997</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Analysis ; Cancer ; Care and treatment ; Decitabine ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Enzymes ; Epigenetic inheritance ; Epigenetics ; Gene expression ; Genes ; Genomes ; Genomics ; Methylation ; Methyltransferases ; Mutation ; Oncology ; Patients ; Retina ; Retinoblastoma ; Scientific equipment industry ; Siblings ; Studies ; Transcription (Genetics) ; Tumors</subject><ispartof>Oncology letters, 2020-07, Vol.20 (1), p.715-723</ispartof><rights>Copyright: © Yazici et al.</rights><rights>COPYRIGHT 2020 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2020</rights><rights>Copyright: © Yazici et al. 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-112a438fc5d001e8d9b03414d60adf0955b444efcc38c03e74317beea255fa043</citedby><cites>FETCH-LOGICAL-c513t-112a438fc5d001e8d9b03414d60adf0955b444efcc38c03e74317beea255fa043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286142/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286142/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32565997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yazici, Hülya</creatorcontrib><creatorcontrib>Wu, Hui-Chen</creatorcontrib><creatorcontrib>Tigli, Hulya</creatorcontrib><creatorcontrib>Yilmaz, Elif Z</creatorcontrib><creatorcontrib>Kebudi, Rejin</creatorcontrib><creatorcontrib>Santella, Regina M</creatorcontrib><title>High levels of global genome methylation in patients with retinoblastoma</title><title>Oncology letters</title><addtitle>Oncol Lett</addtitle><description>Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (
) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (
). Thus, there is a direct interaction between
and
. The present study hypothesized that uncontrolled
and
expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, in
and/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 of
genes 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 of
genes were increased in the WERI-RB-1 cell line, which has a mutated
gene, compared with a wild-type
-expressing cell line. These results supported the hypothesis that epigenetic alterations, as well as mutations in
, may be associated with the oncogenesis and inheritance of retinoblastoma. The repression of genes that interact with
, such as the
gene family, may be important in patients with retinoblastoma with alterations in
, and may serve a role in the treatment and regression of retinoblastoma.</description><subject>Analysis</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Decitabine</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Enzymes</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Methylation</subject><subject>Methyltransferases</subject><subject>Mutation</subject><subject>Oncology</subject><subject>Patients</subject><subject>Retina</subject><subject>Retinoblastoma</subject><subject>Scientific equipment industry</subject><subject>Siblings</subject><subject>Studies</subject><subject>Transcription (Genetics)</subject><subject>Tumors</subject><issn>1792-1074</issn><issn>1792-1082</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkc9rFTEQxxdRbKk9epWA4G2f-b3JRShFfULBi55DNjvZTckmz82-Sv_75tn67AMzhwyZz3yZzLdp3hK8YUrTjzluKKZ4Q4gk7EVzTjpNW4IVfXnMO37WXJZyi-sRkiglXzdnjAoptO7Om-02jBOKcAexoOzRGHNvIxoh5RnQDOt0H-0ackIhoV3NIK0F_Q7rhBZYQ8p9tGXNs33TvPI2Frh8ui-an18-_7jetjffv367vrppnSBsbQmhljPlnRgwJqAG3WPGCR8ktoPHWoiecw7eOaYcZtBxRroewFIhvMWcXTSfHnV3-36GwdV5FhvNbgmzXe5NtsGcVlKYzJjvTEeVJJxWgfdPAkv-tYeymtu8X1Kd2VBOJNZUi-4fNdoIJiSfq5ibQ3HmSjKqOqylqNTmP1SNAebgcgIf6vtJw4dnDRPYuE4lx_1hw-UUbB9Bt-RSFvDHHxJsDt6bHM3Be_PH-8q_e76WI_3XafYAlMOoRw</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Yazici, Hülya</creator><creator>Wu, Hui-Chen</creator><creator>Tigli, Hulya</creator><creator>Yilmaz, Elif Z</creator><creator>Kebudi, Rejin</creator><creator>Santella, Regina M</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20200701</creationdate><title>High levels of global genome methylation in patients with retinoblastoma</title><author>Yazici, Hülya ; Wu, Hui-Chen ; Tigli, Hulya ; Yilmaz, Elif Z ; Kebudi, Rejin ; Santella, Regina M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-112a438fc5d001e8d9b03414d60adf0955b444efcc38c03e74317beea255fa043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Cancer</topic><topic>Care and treatment</topic><topic>Decitabine</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Enzymes</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Methylation</topic><topic>Methyltransferases</topic><topic>Mutation</topic><topic>Oncology</topic><topic>Patients</topic><topic>Retina</topic><topic>Retinoblastoma</topic><topic>Scientific equipment industry</topic><topic>Siblings</topic><topic>Studies</topic><topic>Transcription (Genetics)</topic><topic>Tumors</topic><toplevel>online_resources</toplevel><creatorcontrib>Yazici, Hülya</creatorcontrib><creatorcontrib>Wu, Hui-Chen</creatorcontrib><creatorcontrib>Tigli, Hulya</creatorcontrib><creatorcontrib>Yilmaz, Elif Z</creatorcontrib><creatorcontrib>Kebudi, Rejin</creatorcontrib><creatorcontrib>Santella, Regina M</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yazici, Hülya</au><au>Wu, Hui-Chen</au><au>Tigli, Hulya</au><au>Yilmaz, Elif Z</au><au>Kebudi, Rejin</au><au>Santella, Regina M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High levels of global genome methylation in patients with retinoblastoma</atitle><jtitle>Oncology letters</jtitle><addtitle>Oncol Lett</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>20</volume><issue>1</issue><spage>715</spage><epage>723</epage><pages>715-723</pages><issn>1792-1074</issn><eissn>1792-1082</eissn><abstract>Retinoblastoma is a tumor of the embryonic neural retina in young children. The DNA methyltransferase 1 (
) gene has been demonstrated to be transcriptionally activated in cells lacking retinoblastoma 1 (
). Thus, there is a direct interaction between
and
. The present study hypothesized that uncontrolled
and
expression may lead to a high level of global genome methylation causing a second hit or where both alleles are altered, in
and/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 of
genes 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 of
genes were increased in the WERI-RB-1 cell line, which has a mutated
gene, compared with a wild-type
-expressing cell line. These results supported the hypothesis that epigenetic alterations, as well as mutations in
, may be associated with the oncogenesis and inheritance of retinoblastoma. The repression of genes that interact with
, such as the
gene family, may be important in patients with retinoblastoma with alterations in
, and may serve a role in the treatment and regression of retinoblastoma.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>32565997</pmid><doi>10.3892/ol.2020.11613</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology letters, 2020-07, Vol.20 (1), p.715-723 |
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| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7286142 |
| source | Spandidos Publications Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Analysis Cancer Care and treatment Decitabine Deoxyribonucleic acid DNA DNA methylation Enzymes Epigenetic inheritance Epigenetics Gene expression Genes Genomes Genomics Methylation Methyltransferases Mutation Oncology Patients Retina Retinoblastoma Scientific equipment industry Siblings Studies Transcription (Genetics) Tumors |
| title | High levels of global genome methylation in patients with retinoblastoma |
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