Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?
Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O -methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TE...
Gespeichert in:
Veröffentlicht in: | European journal of cancer (1990) 2021-04, Vol.147, p.84 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | |
---|---|
container_issue | |
container_start_page | 84 |
container_title | European journal of cancer (1990) |
container_volume | 147 |
creator | Gramatzki, Dorothee Felsberg, Jörg Hentschel, Bettina Wolter, Marietta Schackert, Gabriele Westphal, Manfred Regli, Luca Thon, Niklas Tatagiba, Marcos Wick, Wolfgang Schlegel, Uwe Krex, Dietmar Matschke, Jakob Roth, Patrick Suresh, Marian P Kamp, Marcel A Rushing, Elisabeth J Pietsch, Torsten von Deimling, Andreas Sabel, Michael Loeffler, Markus Weller, Michael Reifenberger, Guido |
description | Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O
-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma.
MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302).
In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes.
Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma. |
doi_str_mv | 10.1016/j.ejca.2021.01.014 |
format | Article |
fullrecord | <record><control><sourceid>pubmed</sourceid><recordid>TN_cdi_pubmed_primary_33631540</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>33631540</sourcerecordid><originalsourceid>FETCH-LOGICAL-p108t-89a776092e2a82293f4d2c6d7328df1cda9f2bd107db26e3952a000bcb73e0513</originalsourceid><addsrcrecordid>eNpFkN1Kw0AQhRdBbK2-gBcyL5C4P21-vJFSf6HYm3pdNtlJuzXZDbtbJb6sr2LaKsLAgTOcj5lDyBWjMaMsudnGuC1lzClnMd3P-IQMWZbmEc0mfEDOvd9SStNsTM_IQIhEsMmYDsn3EmvboJMeweEHul6Dk8aXTrdh77bONjagg2YXZNDWRCCNggUkEDUYNl293kmjDcL96xSOzoFQHan_-cPqiGhQaRlQgUfjddAfOnQQLARs7JftL9IKQRvQ3pa6pwUEhZtOObtG01OjT12rKHQtwrrWtqilD7aRt30AwgYdgoRam_e7C3Jaydrj5a-OyNvjw3L2HM0XTy-z6TxqGc1ClOUyTROac-Qy4zwX1VjxMlGp4JmqWKlkXvFCMZqqgico8gmXfZ1FWaQC6YSJEbk-cttd0T-3ap1upOtWf02LH_QHh4I</addsrcrecordid><sourcetype>Index Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?</title><source>Elsevier ScienceDirect Journals</source><creator>Gramatzki, Dorothee ; Felsberg, Jörg ; Hentschel, Bettina ; Wolter, Marietta ; Schackert, Gabriele ; Westphal, Manfred ; Regli, Luca ; Thon, Niklas ; Tatagiba, Marcos ; Wick, Wolfgang ; Schlegel, Uwe ; Krex, Dietmar ; Matschke, Jakob ; Roth, Patrick ; Suresh, Marian P ; Kamp, Marcel A ; Rushing, Elisabeth J ; Pietsch, Torsten ; von Deimling, Andreas ; Sabel, Michael ; Loeffler, Markus ; Weller, Michael ; Reifenberger, Guido</creator><creatorcontrib>Gramatzki, Dorothee ; Felsberg, Jörg ; Hentschel, Bettina ; Wolter, Marietta ; Schackert, Gabriele ; Westphal, Manfred ; Regli, Luca ; Thon, Niklas ; Tatagiba, Marcos ; Wick, Wolfgang ; Schlegel, Uwe ; Krex, Dietmar ; Matschke, Jakob ; Roth, Patrick ; Suresh, Marian P ; Kamp, Marcel A ; Rushing, Elisabeth J ; Pietsch, Torsten ; von Deimling, Andreas ; Sabel, Michael ; Loeffler, Markus ; Weller, Michael ; Reifenberger, Guido</creatorcontrib><description>Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O
-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma.
MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302).
In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes.
Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma.</description><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2021.01.014</identifier><identifier>PMID: 33631540</identifier><language>eng</language><publisher>England</publisher><ispartof>European journal of cancer (1990), 2021-04, Vol.147, p.84</ispartof><rights>Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33631540$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gramatzki, Dorothee</creatorcontrib><creatorcontrib>Felsberg, Jörg</creatorcontrib><creatorcontrib>Hentschel, Bettina</creatorcontrib><creatorcontrib>Wolter, Marietta</creatorcontrib><creatorcontrib>Schackert, Gabriele</creatorcontrib><creatorcontrib>Westphal, Manfred</creatorcontrib><creatorcontrib>Regli, Luca</creatorcontrib><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Tatagiba, Marcos</creatorcontrib><creatorcontrib>Wick, Wolfgang</creatorcontrib><creatorcontrib>Schlegel, Uwe</creatorcontrib><creatorcontrib>Krex, Dietmar</creatorcontrib><creatorcontrib>Matschke, Jakob</creatorcontrib><creatorcontrib>Roth, Patrick</creatorcontrib><creatorcontrib>Suresh, Marian P</creatorcontrib><creatorcontrib>Kamp, Marcel A</creatorcontrib><creatorcontrib>Rushing, Elisabeth J</creatorcontrib><creatorcontrib>Pietsch, Torsten</creatorcontrib><creatorcontrib>von Deimling, Andreas</creatorcontrib><creatorcontrib>Sabel, Michael</creatorcontrib><creatorcontrib>Loeffler, Markus</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><creatorcontrib>Reifenberger, Guido</creatorcontrib><title>Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O
-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma.
MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302).
In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes.
Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma.</description><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpFkN1Kw0AQhRdBbK2-gBcyL5C4P21-vJFSf6HYm3pdNtlJuzXZDbtbJb6sr2LaKsLAgTOcj5lDyBWjMaMsudnGuC1lzClnMd3P-IQMWZbmEc0mfEDOvd9SStNsTM_IQIhEsMmYDsn3EmvboJMeweEHul6Dk8aXTrdh77bONjagg2YXZNDWRCCNggUkEDUYNl293kmjDcL96xSOzoFQHan_-cPqiGhQaRlQgUfjddAfOnQQLARs7JftL9IKQRvQ3pa6pwUEhZtOObtG01OjT12rKHQtwrrWtqilD7aRt30AwgYdgoRam_e7C3Jaydrj5a-OyNvjw3L2HM0XTy-z6TxqGc1ClOUyTROac-Qy4zwX1VjxMlGp4JmqWKlkXvFCMZqqgico8gmXfZ1FWaQC6YSJEbk-cttd0T-3ap1upOtWf02LH_QHh4I</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Gramatzki, Dorothee</creator><creator>Felsberg, Jörg</creator><creator>Hentschel, Bettina</creator><creator>Wolter, Marietta</creator><creator>Schackert, Gabriele</creator><creator>Westphal, Manfred</creator><creator>Regli, Luca</creator><creator>Thon, Niklas</creator><creator>Tatagiba, Marcos</creator><creator>Wick, Wolfgang</creator><creator>Schlegel, Uwe</creator><creator>Krex, Dietmar</creator><creator>Matschke, Jakob</creator><creator>Roth, Patrick</creator><creator>Suresh, Marian P</creator><creator>Kamp, Marcel A</creator><creator>Rushing, Elisabeth J</creator><creator>Pietsch, Torsten</creator><creator>von Deimling, Andreas</creator><creator>Sabel, Michael</creator><creator>Loeffler, Markus</creator><creator>Weller, Michael</creator><creator>Reifenberger, Guido</creator><scope>NPM</scope></search><sort><creationdate>202104</creationdate><title>Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?</title><author>Gramatzki, Dorothee ; Felsberg, Jörg ; Hentschel, Bettina ; Wolter, Marietta ; Schackert, Gabriele ; Westphal, Manfred ; Regli, Luca ; Thon, Niklas ; Tatagiba, Marcos ; Wick, Wolfgang ; Schlegel, Uwe ; Krex, Dietmar ; Matschke, Jakob ; Roth, Patrick ; Suresh, Marian P ; Kamp, Marcel A ; Rushing, Elisabeth J ; Pietsch, Torsten ; von Deimling, Andreas ; Sabel, Michael ; Loeffler, Markus ; Weller, Michael ; Reifenberger, Guido</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p108t-89a776092e2a82293f4d2c6d7328df1cda9f2bd107db26e3952a000bcb73e0513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gramatzki, Dorothee</creatorcontrib><creatorcontrib>Felsberg, Jörg</creatorcontrib><creatorcontrib>Hentschel, Bettina</creatorcontrib><creatorcontrib>Wolter, Marietta</creatorcontrib><creatorcontrib>Schackert, Gabriele</creatorcontrib><creatorcontrib>Westphal, Manfred</creatorcontrib><creatorcontrib>Regli, Luca</creatorcontrib><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Tatagiba, Marcos</creatorcontrib><creatorcontrib>Wick, Wolfgang</creatorcontrib><creatorcontrib>Schlegel, Uwe</creatorcontrib><creatorcontrib>Krex, Dietmar</creatorcontrib><creatorcontrib>Matschke, Jakob</creatorcontrib><creatorcontrib>Roth, Patrick</creatorcontrib><creatorcontrib>Suresh, Marian P</creatorcontrib><creatorcontrib>Kamp, Marcel A</creatorcontrib><creatorcontrib>Rushing, Elisabeth J</creatorcontrib><creatorcontrib>Pietsch, Torsten</creatorcontrib><creatorcontrib>von Deimling, Andreas</creatorcontrib><creatorcontrib>Sabel, Michael</creatorcontrib><creatorcontrib>Loeffler, Markus</creatorcontrib><creatorcontrib>Weller, Michael</creatorcontrib><creatorcontrib>Reifenberger, Guido</creatorcontrib><collection>PubMed</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gramatzki, Dorothee</au><au>Felsberg, Jörg</au><au>Hentschel, Bettina</au><au>Wolter, Marietta</au><au>Schackert, Gabriele</au><au>Westphal, Manfred</au><au>Regli, Luca</au><au>Thon, Niklas</au><au>Tatagiba, Marcos</au><au>Wick, Wolfgang</au><au>Schlegel, Uwe</au><au>Krex, Dietmar</au><au>Matschke, Jakob</au><au>Roth, Patrick</au><au>Suresh, Marian P</au><au>Kamp, Marcel A</au><au>Rushing, Elisabeth J</au><au>Pietsch, Torsten</au><au>von Deimling, Andreas</au><au>Sabel, Michael</au><au>Loeffler, Markus</au><au>Weller, Michael</au><au>Reifenberger, Guido</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link?</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2021-04</date><risdate>2021</risdate><volume>147</volume><spage>84</spage><pages>84-</pages><eissn>1879-0852</eissn><abstract>Benefit from temozolomide (TMZ) chemotherapy in the treatment of isocitrate dehydrogenase (IDH)-wild-type glioblastoma is essentially limited to patients with O
-methylguanine DNA methyltransferase (MGMT) promoter-methylated tumours. Recent studies suggested that telomerase reverse transcriptase (TERT) promoter hotspot mutations may have an impact on the prognostic role of the MGMT status in patients with glioblastoma.
MGMT promoter methylation and TERT promoter mutation status were retrospectively assessed in a prospective cohort of patients with IDH-wild-type glioblastoma of the German Glioma Network (GGN) (n = 298) and an independent retrospective cohort from Düsseldorf, Germany, and Zurich, Switzerland (n = 302).
In the GGN cohort, but not in the Düsseldorf/Zurich cohort, TERT promoter mutation was moderately associated with inferior outcomes in patients with MGMT promoter-unmethylated tumours (hazard ratio 1.74; 95% confidence interval: 1.07-2.82; p = 0.026). TERT promoter mutations were not associated with better outcomes in patients with MGMT promoter-methylated tumours in either cohort. The two different TERT promoter hotspot mutations (C228T and C250T) were not linked to distinct outcomes.
Analysis of two independent cohorts of patients with glioblastoma did not confirm previous data, suggesting that TERT promoter mutations confer an enhanced benefit from TMZ in patients with MGMT promoter-methylated glioblastoma. Thus, diagnostic testing for TERT promoter mutations may not be required for prediction of TMZ sensitivity in patients with IDH-wild-type glioblastoma.</abstract><cop>England</cop><pmid>33631540</pmid><doi>10.1016/j.ejca.2021.01.014</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | EISSN: 1879-0852 |
ispartof | European journal of cancer (1990), 2021-04, Vol.147, p.84 |
issn | 1879-0852 |
language | eng |
recordid | cdi_pubmed_primary_33631540 |
source | Elsevier ScienceDirect Journals |
title | Telomerase reverse transcriptase promoter mutation- and O 6 -methylguanine DNA methyltransferase promoter methylation-mediated sensitivity to temozolomide in isocitrate dehydrogenase-wild-type glioblastoma: is there a link? |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T03%3A23%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Telomerase%20reverse%20transcriptase%20promoter%20mutation-%20and%20O%206%20-methylguanine%20DNA%20methyltransferase%20promoter%20methylation-mediated%20sensitivity%20to%20temozolomide%20in%20isocitrate%20dehydrogenase-wild-type%20glioblastoma:%20is%20there%20a%20link?&rft.jtitle=European%20journal%20of%20cancer%20(1990)&rft.au=Gramatzki,%20Dorothee&rft.date=2021-04&rft.volume=147&rft.spage=84&rft.pages=84-&rft.eissn=1879-0852&rft_id=info:doi/10.1016/j.ejca.2021.01.014&rft_dat=%3Cpubmed%3E33631540%3C/pubmed%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33631540&rfr_iscdi=true |