T2-FLAIR 错配信号预测 IDH 突变星形细胞瘤中的 DNA 甲基化亚类和 CDKN2A/B 状态。
T2-FLAIR Mismatch Sign Predicts DNA Methylation Subclass and CDKN2A/B Status in IDH-Mutant Astrocytomas.
机构信息
Department of Radiology, NYU Grossman School of Medicine, New York, New York.
Department of Neurosurgery, NYU Grossman School of Medicine, New York, New York.
出版信息
Clin Cancer Res. 2024 Aug 15;30(16):3512-3519. doi: 10.1158/1078-0432.CCR-24-0311.
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.
目的
DNA 甲基化分析将异柠檬酸脱氢酶（IDH）突变型星形细胞瘤分为甲基化低级别和高级别组。我们根据 2021 年世界卫生组织分类，研究了 T2 液体衰减反转恢复（T2-FLAIR）失配信号在预测 DNA 甲基化级别和细胞周期蛋白依赖性激酶抑制剂 2A/B（CDKN2A/B）纯合缺失（IDH 突变型星形细胞瘤 4 级的分子生物标志物）方面的应用。
实验设计
对 DNA 甲基化谱分类的 IDH 突变型星形细胞瘤的术前 MRI 扫描（n=71）由两名放射科医生独立评估 T2-FLAIR 失配信号。分析 T2-FLAIR 失配在预测甲基化级别、CDKN2A/B 状态、拷贝数变异和生存方面的诊断效用。
结果
45 例甲基化低级别病例中有 21 例（46.7%）和 26 例甲基化高级别病例中有 1 例（3.9%）存在 T2-FLAIR 失配信号（P<0.001），特异性为 96.2%，阳性预测值为 95.5%，阴性预测值为 51.0%，用于预测低甲基化级别。T2-FLAIR 失配信号也与完整的 CDKN2A/B 状态显著相关（P=0.028），特异性为 87.5%，阳性预测值为 86.4%，阴性预测值为 42.9%。总体多变量 Cox 分析显示，保留的 CDKN2A/B 状态与无进展生存率相关（P=0.01）。对 CDKN2A/B 状态、拷贝数变异和甲基化级别几乎平分的组织学 3 级亚组进行多变量 Cox 分析，结果显示 DNA 甲基化级别与总生存率相关（P=0.045），CDKN2A/B 状态与无进展生存率相关（P=0.052）有趋势。
结论
T2-FLAIR 失配信号对 IDH 突变型星形细胞瘤的低甲基化级别和完整的 CDKN2A/B 具有高度特异性。
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