EPCO-31. THE GERMLINE POLYMORPHISM RS55705857 IS ASSOCIATED WITH A POOR SURVIVAL IN ASTROCYTOMA, IDH-MUTANT, GRADE 2
Abstract Histologic features, presence of CDKN2A/B homozygous deletion and methylation subtype are strong determinants of outcome and of therapy in IDH-mutant gliomas. We were interested in learning if there are additional markers of outcome in these tumors. To address this question, we assembled a...
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| Veröffentlicht in: | Neuro-oncology (Charlottesville, Va.) Va.), 2024-11, Vol.26 (Supplement_8), p.viii8-viii8 |
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| creator | Drucker, Kristen L Kollmeyer, Thomas M Decker, Paul A Kosel, Matthew L Odukoya, Lateef A Sarkar, Gobinda Halder, Chandralekha De Lorenzo, Silvana B Burns, Terry C Giannini, Caterina Ida, Cristiane M Lachance, Daniel H Eckel-Passow, Jeanette E Jenkins, Robert B |
| description | Abstract
Histologic features, presence of CDKN2A/B homozygous deletion and methylation subtype are strong determinants of outcome and of therapy in IDH-mutant gliomas. We were interested in learning if there are additional markers of outcome in these tumors. To address this question, we assembled a cohort of 963 IDH-mutant gliomas with overall survival data (median follow-up alive 2.7 years, median follow-up deceased 3.9 years). Array-based copy number data, targeted NGS, germline genotyping data and Illumina EPIC array methylation data were available on 872, 226, 542, and 401 patients, respectively. Morphologic type (oligodendroglioma versus astrocytoma, grade (2/3 vs 4) and methylation subtype (A_IDH_LG vs A_IDH_HG) were all significantly associated with survival (p |
| doi_str_mv | 10.1093/neuonc/noae165.0030 |
| format | Article |
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Histologic features, presence of CDKN2A/B homozygous deletion and methylation subtype are strong determinants of outcome and of therapy in IDH-mutant gliomas. We were interested in learning if there are additional markers of outcome in these tumors. To address this question, we assembled a cohort of 963 IDH-mutant gliomas with overall survival data (median follow-up alive 2.7 years, median follow-up deceased 3.9 years). Array-based copy number data, targeted NGS, germline genotyping data and Illumina EPIC array methylation data were available on 872, 226, 542, and 401 patients, respectively. Morphologic type (oligodendroglioma versus astrocytoma, grade (2/3 vs 4) and methylation subtype (A_IDH_LG vs A_IDH_HG) were all significantly associated with survival (p <0.001). There was no significant difference in survival between grade 2 vs 3 IDH-mutant astrocytomas (p=0.53 adjusting for age and sex). However, subjects with the risk allele (G) for rs55705857 had a better overall survival than subjects with the non-risk allele (A) in IDH-mutant oligodendroglioma (AG/GG vs AA, median overall survival 21.6 vs 15.7 years, p=0.048 after adjusting for grade, age, and sex). Conversely, rs55705857 was associated with a markedly worse survival in grade 2 IDH-mutant astrocytomas (AG/GG vs AA, median overall survival 8.6 vs 19.6 years, p=0.007 after adjusting for age and sex). Despite similar sample sizes and number of deaths, there was no significant difference in overall survival by rs55705857 genotype in grade 3 or 4 IDH-mutant astrocytomas. Upon further functional analyses, TLX1 and GALNT17 were found to be differentially methylated in IDH1-mutant astrocytomas and oligodendrogliomas, respectively, when stratified by rs55705857 risk allele. This is the first observation of a germline characteristic (e.g. rs55705857) predicting survival in low-grade IDH-mutant astrocytoma. While this observation requires validation, it suggests that germline genotype may be practice changing and inform results of trials such as CATNON and CODEL.</description><identifier>ISSN: 1522-8517</identifier><identifier>EISSN: 1523-5866</identifier><identifier>DOI: 10.1093/neuonc/noae165.0030</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><ispartof>Neuro-oncology (Charlottesville, Va.), 2024-11, Vol.26 (Supplement_8), p.viii8-viii8</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Drucker, Kristen L</creatorcontrib><creatorcontrib>Kollmeyer, Thomas M</creatorcontrib><creatorcontrib>Decker, Paul A</creatorcontrib><creatorcontrib>Kosel, Matthew L</creatorcontrib><creatorcontrib>Odukoya, Lateef A</creatorcontrib><creatorcontrib>Sarkar, Gobinda</creatorcontrib><creatorcontrib>Halder, Chandralekha</creatorcontrib><creatorcontrib>De Lorenzo, Silvana B</creatorcontrib><creatorcontrib>Burns, Terry C</creatorcontrib><creatorcontrib>Giannini, Caterina</creatorcontrib><creatorcontrib>Ida, Cristiane M</creatorcontrib><creatorcontrib>Lachance, Daniel H</creatorcontrib><creatorcontrib>Eckel-Passow, Jeanette E</creatorcontrib><creatorcontrib>Jenkins, Robert B</creatorcontrib><title>EPCO-31. THE GERMLINE POLYMORPHISM RS55705857 IS ASSOCIATED WITH A POOR SURVIVAL IN ASTROCYTOMA, IDH-MUTANT, GRADE 2</title><title>Neuro-oncology (Charlottesville, Va.)</title><description>Abstract
Histologic features, presence of CDKN2A/B homozygous deletion and methylation subtype are strong determinants of outcome and of therapy in IDH-mutant gliomas. We were interested in learning if there are additional markers of outcome in these tumors. To address this question, we assembled a cohort of 963 IDH-mutant gliomas with overall survival data (median follow-up alive 2.7 years, median follow-up deceased 3.9 years). Array-based copy number data, targeted NGS, germline genotyping data and Illumina EPIC array methylation data were available on 872, 226, 542, and 401 patients, respectively. Morphologic type (oligodendroglioma versus astrocytoma, grade (2/3 vs 4) and methylation subtype (A_IDH_LG vs A_IDH_HG) were all significantly associated with survival (p <0.001). There was no significant difference in survival between grade 2 vs 3 IDH-mutant astrocytomas (p=0.53 adjusting for age and sex). However, subjects with the risk allele (G) for rs55705857 had a better overall survival than subjects with the non-risk allele (A) in IDH-mutant oligodendroglioma (AG/GG vs AA, median overall survival 21.6 vs 15.7 years, p=0.048 after adjusting for grade, age, and sex). Conversely, rs55705857 was associated with a markedly worse survival in grade 2 IDH-mutant astrocytomas (AG/GG vs AA, median overall survival 8.6 vs 19.6 years, p=0.007 after adjusting for age and sex). Despite similar sample sizes and number of deaths, there was no significant difference in overall survival by rs55705857 genotype in grade 3 or 4 IDH-mutant astrocytomas. Upon further functional analyses, TLX1 and GALNT17 were found to be differentially methylated in IDH1-mutant astrocytomas and oligodendrogliomas, respectively, when stratified by rs55705857 risk allele. This is the first observation of a germline characteristic (e.g. rs55705857) predicting survival in low-grade IDH-mutant astrocytoma. While this observation requires validation, it suggests that germline genotype may be practice changing and inform results of trials such as CATNON and CODEL.</description><issn>1522-8517</issn><issn>1523-5866</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqNkEFOwzAQRS0EEqVwAjY-QJPace0kSys1jaWkrhK3qKvIDo4EgqZK6ILb49IegNWMZv4f_XkAPGMUYpSS-cGd-kM7P_TGYUZDhAi6ARNMIxLQhLHbvz4KEorje_Awjh8IRZgyPAHfYpOpgOAQ6lzAlajKQq4F3KhiX6pqk8u6hFVNaYxoQmMoa8jrWmWSa7GEr1LnkHuxqmC9rXZyxwso116iK5XttSr5DMplHpRbzdd6BlcVXwoYPYK7znyO7ulap0C_CJ3lQaFWMuNF0CYEBYuYMmdSm_jsqWV4YayNbecHbeKQYwlLbWdxHL1hv44MiV1nOkNpxPx3hpIpIJez7dCP4-C65ji8f5nhp8GoOXNrLtyaK7fmzM27wourPx3_ZfgF7mlpCQ</recordid><startdate>20241111</startdate><enddate>20241111</enddate><creator>Drucker, Kristen L</creator><creator>Kollmeyer, Thomas M</creator><creator>Decker, Paul A</creator><creator>Kosel, Matthew L</creator><creator>Odukoya, Lateef A</creator><creator>Sarkar, Gobinda</creator><creator>Halder, Chandralekha</creator><creator>De Lorenzo, Silvana B</creator><creator>Burns, Terry C</creator><creator>Giannini, Caterina</creator><creator>Ida, Cristiane M</creator><creator>Lachance, Daniel H</creator><creator>Eckel-Passow, Jeanette E</creator><creator>Jenkins, Robert B</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20241111</creationdate><title>EPCO-31. THE GERMLINE POLYMORPHISM RS55705857 IS ASSOCIATED WITH A POOR SURVIVAL IN ASTROCYTOMA, IDH-MUTANT, GRADE 2</title><author>Drucker, Kristen L ; Kollmeyer, Thomas M ; Decker, Paul A ; Kosel, Matthew L ; Odukoya, Lateef A ; Sarkar, Gobinda ; Halder, Chandralekha ; De Lorenzo, Silvana B ; Burns, Terry C ; Giannini, Caterina ; Ida, Cristiane M ; Lachance, Daniel H ; Eckel-Passow, Jeanette E ; Jenkins, Robert B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c830-4756ea9b81529b614abb7bf9b8c8e0e6869bfb172d19b62a37efafa5526021a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Drucker, Kristen L</creatorcontrib><creatorcontrib>Kollmeyer, Thomas M</creatorcontrib><creatorcontrib>Decker, Paul A</creatorcontrib><creatorcontrib>Kosel, Matthew L</creatorcontrib><creatorcontrib>Odukoya, Lateef A</creatorcontrib><creatorcontrib>Sarkar, Gobinda</creatorcontrib><creatorcontrib>Halder, Chandralekha</creatorcontrib><creatorcontrib>De Lorenzo, Silvana B</creatorcontrib><creatorcontrib>Burns, Terry C</creatorcontrib><creatorcontrib>Giannini, Caterina</creatorcontrib><creatorcontrib>Ida, Cristiane M</creatorcontrib><creatorcontrib>Lachance, Daniel H</creatorcontrib><creatorcontrib>Eckel-Passow, Jeanette E</creatorcontrib><creatorcontrib>Jenkins, Robert B</creatorcontrib><collection>CrossRef</collection><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Drucker, Kristen L</au><au>Kollmeyer, Thomas M</au><au>Decker, Paul A</au><au>Kosel, Matthew L</au><au>Odukoya, Lateef A</au><au>Sarkar, Gobinda</au><au>Halder, Chandralekha</au><au>De Lorenzo, Silvana B</au><au>Burns, Terry C</au><au>Giannini, Caterina</au><au>Ida, Cristiane M</au><au>Lachance, Daniel H</au><au>Eckel-Passow, Jeanette E</au><au>Jenkins, Robert B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>EPCO-31. THE GERMLINE POLYMORPHISM RS55705857 IS ASSOCIATED WITH A POOR SURVIVAL IN ASTROCYTOMA, IDH-MUTANT, GRADE 2</atitle><jtitle>Neuro-oncology (Charlottesville, Va.)</jtitle><date>2024-11-11</date><risdate>2024</risdate><volume>26</volume><issue>Supplement_8</issue><spage>viii8</spage><epage>viii8</epage><pages>viii8-viii8</pages><issn>1522-8517</issn><eissn>1523-5866</eissn><abstract>Abstract
Histologic features, presence of CDKN2A/B homozygous deletion and methylation subtype are strong determinants of outcome and of therapy in IDH-mutant gliomas. We were interested in learning if there are additional markers of outcome in these tumors. To address this question, we assembled a cohort of 963 IDH-mutant gliomas with overall survival data (median follow-up alive 2.7 years, median follow-up deceased 3.9 years). Array-based copy number data, targeted NGS, germline genotyping data and Illumina EPIC array methylation data were available on 872, 226, 542, and 401 patients, respectively. Morphologic type (oligodendroglioma versus astrocytoma, grade (2/3 vs 4) and methylation subtype (A_IDH_LG vs A_IDH_HG) were all significantly associated with survival (p <0.001). There was no significant difference in survival between grade 2 vs 3 IDH-mutant astrocytomas (p=0.53 adjusting for age and sex). However, subjects with the risk allele (G) for rs55705857 had a better overall survival than subjects with the non-risk allele (A) in IDH-mutant oligodendroglioma (AG/GG vs AA, median overall survival 21.6 vs 15.7 years, p=0.048 after adjusting for grade, age, and sex). Conversely, rs55705857 was associated with a markedly worse survival in grade 2 IDH-mutant astrocytomas (AG/GG vs AA, median overall survival 8.6 vs 19.6 years, p=0.007 after adjusting for age and sex). Despite similar sample sizes and number of deaths, there was no significant difference in overall survival by rs55705857 genotype in grade 3 or 4 IDH-mutant astrocytomas. Upon further functional analyses, TLX1 and GALNT17 were found to be differentially methylated in IDH1-mutant astrocytomas and oligodendrogliomas, respectively, when stratified by rs55705857 risk allele. This is the first observation of a germline characteristic (e.g. rs55705857) predicting survival in low-grade IDH-mutant astrocytoma. While this observation requires validation, it suggests that germline genotype may be practice changing and inform results of trials such as CATNON and CODEL.</abstract><cop>US</cop><pub>Oxford University Press</pub><doi>10.1093/neuonc/noae165.0030</doi></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| title | EPCO-31. THE GERMLINE POLYMORPHISM RS55705857 IS ASSOCIATED WITH A POOR SURVIVAL IN ASTROCYTOMA, IDH-MUTANT, GRADE 2 |
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