Matthew D Lee, Rajan Jain, Kristyn Galbraith, Anna Chen, Evan Lieberman, Sohil H Patel, Dimitris G Placantonakis, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, John G Golfinos, Daniel A Orringer, Matija Snuderl
{"title":"T2-FLAIR错配标志可预测IDH突变星形细胞瘤的DNA甲基化亚类和CDKN2A/B状态。","authors":"Matthew D Lee, Rajan Jain, Kristyn Galbraith, Anna Chen, Evan Lieberman, Sohil H Patel, Dimitris G Placantonakis, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, John G Golfinos, Daniel A Orringer, Matija Snuderl","doi":"10.1158/1078-0432.CCR-24-0311","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification.</p><p><strong>Experimental design: </strong>Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed.</p><p><strong>Results: </strong>The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052).</p><p><strong>Conclusions: </strong>The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.</p>","PeriodicalId":10279,"journal":{"name":"Clinical Cancer Research","volume":null,"pages":null},"PeriodicalIF":10.0000,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326959/pdf/","citationCount":"0","resultStr":"{\"title\":\"T2-FLAIR Mismatch Sign Predicts DNA Methylation Subclass and CDKN2A/B Status in IDH-Mutant Astrocytomas.\",\"authors\":\"Matthew D Lee, Rajan Jain, Kristyn Galbraith, Anna Chen, Evan Lieberman, Sohil H Patel, Dimitris G Placantonakis, David Zagzag, Marissa Barbaro, Maria Del Pilar Guillermo Prieto Eibl, John G Golfinos, Daniel A Orringer, Matija Snuderl\",\"doi\":\"10.1158/1078-0432.CCR-24-0311\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification.</p><p><strong>Experimental design: </strong>Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed.</p><p><strong>Results: </strong>The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052).</p><p><strong>Conclusions: </strong>The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.</p>\",\"PeriodicalId\":10279,\"journal\":{\"name\":\"Clinical Cancer Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":10.0000,\"publicationDate\":\"2024-08-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11326959/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1078-0432.CCR-24-0311\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1078-0432.CCR-24-0311","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
T2-FLAIR Mismatch Sign Predicts DNA Methylation Subclass and CDKN2A/B Status in IDH-Mutant Astrocytomas.
Purpose: DNA methylation profiling stratifies isocitrate dehydrogenase (IDH)-mutant astrocytomas into methylation low- and high-grade groups. We investigated the utility of the T2-fluid-attenuated inversion recovery (T2-FLAIR) mismatch sign for predicting DNA methylation grade and cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) homozygous deletion, a molecular biomarker for grade 4 IDH-mutant astrocytomas, according to the 2021 World Health Organization classification.
Experimental design: Preoperative MRI scans of IDH-mutant astrocytomas subclassified by DNA methylation profiling (n = 71) were independently evaluated by two radiologists for the T2-FLAIR mismatch sign. The diagnostic utility of T2-FLAIR mismatch in predicting methylation grade, CDKN2A/B status, copy number variation, and survival was analyzed.
Results: The T2-FLAIR mismatch sign was present in 21 of 45 (46.7%) methylation low-grade and 1 of 26 (3.9%) methylation high-grade cases (P < 0.001), resulting in 96.2% specificity, 95.5% positive predictive value, and 51.0% negative predictive value for predicting low methylation grade. The T2-FLAIR mismatch sign was also significantly associated with intact CDKN2A/B status (P = 0.028) with 87.5% specificity, 86.4% positive predictive value, and 42.9% negative predictive value. Overall multivariable Cox analysis showed that retained CDKN2A/B status remained significant for progression-free survival (P = 0.01). Multivariable Cox analysis of the histologic grade 3 subset, which was nearly evenly divided by CDKN2A/B status, copy number variation, and methylation grade, showed trends toward significance for DNA methylation grade with overall survival (P = 0.045) and CDKN2A/B status with progression-free survival (P = 0.052).
Conclusions: The T2-FLAIR mismatch sign is highly specific for low methylation grade and intact CDKN2A/B in IDH-mutant astrocytomas.
期刊介绍:
Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.