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DNA甲基化在临床实践中为脑膜瘤复发提供诊断价值。

DNA methylation provides diagnostic value for meningioma recurrence in clinical practice.

作者信息

Shen Erica, Leclair Nathan K, Herlth Kristi, Soucy Melissa, Renzette Nick, Zhuo Xinming, Kelly Kevin, Omerza Gregory, Onyiuke Hilary, McNeill Ian, Wolansky Leo, Becker Kevin, Li Lei, Wu Qian, Bulsara Ketan R

机构信息

Division of Neurosurgery, Department of Surgery, UConn Health, 263 Farmington Ave, Farmington, CT, 06030, USA.

The Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, 06030, USA.

出版信息

Acta Neurochir (Wien). 2023 May;165(5):1323-1331. doi: 10.1007/s00701-023-05550-5. Epub 2023 Mar 15.

Abstract

BACKGROUND

Meningiomas are the most common intracranial tumors. Recent advancements in the genetic profiling of tumors have allowed information including DNA copy number analysis, mutational analysis, and RNA sequencing to be more frequently reported, in turn allowing better characterization of meningiomas. In recent years, analysis of tumor methylomes that reflects both cell-origin methylation signatures and somatically acquired DNA methylation changes has been utilized to better classify meningiomas with great success.

METHOD

We report DNA methylation profiling on meningiomas from 17 patients. Formalin-fixed paraffin-embedded (FFPE) meningioma tumor samples were processed, loaded onto the Infinium Methylation EPIC array, and scanned using the Illumina IScan system. Raw IDAT files were processed through the the CNS tumor classifier developed by the Molecular Neuropathology group at the German Cancer Research Center (DKFZ). Corresponding genomics were captured using targeted sequencing panels.

RESULT

Among the meningioma samples, 13 samples were classified as "benign," two samples as "intermediate," and the remaining three samples (from two patients) as "malignant," based on previously validated classification algorithms. In addition to tumor methylation profiling, we also present information that includes patient demographics, clinical presentations, tumor characteristics (including size and location), surgical approaches, and mutational analysis. The two patients who provided the samples with "malignant" methylation classifications had tumor recurrence, reflecting a more aggressive disease course.

CONCLUSION

In accordance with prior reports, our case series provides support that tumor DNA methylation profiling adds meaningful classification information and may be beneficial to incorporate in clinical practice. Our report also reveals that DNA methylation combined with WHO histology classification can more accurately predict tumor behavior than WHO classification alone.

摘要

背景

脑膜瘤是最常见的颅内肿瘤。肿瘤基因谱分析的最新进展使得包括DNA拷贝数分析、突变分析和RNA测序等信息报告得更为频繁,进而能够更好地表征脑膜瘤。近年来,反映细胞起源甲基化特征和体细胞获得性DNA甲基化变化的肿瘤甲基化组分析已被用于更好地对脑膜瘤进行分类,并取得了巨大成功。

方法

我们报告了17例脑膜瘤患者的DNA甲基化谱分析结果。对福尔马林固定石蜡包埋(FFPE)的脑膜瘤肿瘤样本进行处理,加载到Infinium甲基化EPIC芯片上,并使用Illumina IScan系统进行扫描。原始IDAT文件通过德国癌症研究中心(DKFZ)分子神经病理学小组开发的中枢神经系统肿瘤分类器进行处理。使用靶向测序面板捕获相应的基因组信息。

结果

根据先前验证的分类算法,在脑膜瘤样本中,13个样本被分类为“良性”,2个样本为“中间型”,其余3个样本(来自2名患者)为“恶性”。除了肿瘤甲基化谱分析外,我们还提供了包括患者人口统计学、临床表现、肿瘤特征(包括大小和位置)、手术方法和突变分析等信息。提供“恶性”甲基化分类样本的两名患者出现了肿瘤复发,反映出疾病进程更具侵袭性。

结论

与先前的报告一致,我们的病例系列支持肿瘤DNA甲基化谱分析增加了有意义的分类信息,可能有利于纳入临床实践。我们的报告还表明,与仅使用世界卫生组织(WHO)组织学分类相比,DNA甲基化结合WHO组织学分类能够更准确地预测肿瘤行为。

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