Mihaela Chirica, Philipp Jurmeister, Daniel Teichmann, Arend Koch, Eilís Perez, Simone Schmid, Michèle Simon, Pablo Hernáiz Driever, Carina Bodden, Cornelis M van Tilburg, Emily C Hardin, Cinzia Lavarino, Jürgen Hench, David Scheie, Jane Cryan, Ales Vicha, Francesca R Buttarelli, An Michiels, Christine Haberler, Paulette Barahona, Bastiaan B J Tops, Tom Jacques, Tore Stokland, Olaf Witt, David T W Jones, David Capper
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引用次数: 0
Abstract
Aims: DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions.
Methods: Four representative low-grade gliomas of distinct histologies were centrally selected, and DNA extraction was performed. Participating laboratories received a DNA aliquot and performed the DNA methylation-based classification and result interpretation without knowledge of tumour histology. Additionally, participants were required to interpret the copy number profile derived from DNA methylation data and conduct DNA sequencing of the BRAF hotspot p.V600 due to its relevance for low-grade gliomas. Results had to be returned within 30 days.
Results: High technical reproducibility was observed, with a median pairwise correlation of 0.99 (range 0.94-0.99) between coordinating laboratory and participants. DNA methylation-based tumour classification and copy number profile interpretation were consistent across all centres, and BRAF mutation status was accurately reported for all cases. Eleven out of 12 centres successfully reported their analysis within the 30-day timeframe.
Conclusion: Our study demonstrates remarkable concordance in DNA methylation profiling and profile interpretation across 12 international centres. These findings underscore the potential contribution of DNA methylation analysis to the harmonisation of brain tumour diagnostics.
DNA 甲基化阵列实验室间比较试验表明，13 个国际中心的儿科中枢神经系统肿瘤分类具有高度的可重复性。
目的：DNA 甲基化分析最近被世界卫生组织（WHO）认可为脑肿瘤的关键诊断工具，其最常见的方法是使用珠子阵列。尽管该方法被广泛使用，但有关其技术可重复性和潜在跨机构差异的数据却十分有限。LOGGIC 核心生物临床数据库注册中心与 12 家国际实验室开展了一项前瞻性实验室比较试验，以提高儿科低级别胶质瘤的诊断准确性，重点关注临床实时条件下 DNA 甲基化数据生成和图谱解读的技术方面：方法：集中选取四种不同组织学的代表性低级别胶质瘤，并进行 DNA 提取。方法：集中选取四种不同组织学的代表性低级别胶质瘤并进行 DNA 提取，参与实验室收到 DNA 等分，在不了解肿瘤组织学的情况下进行基于 DNA 甲基化的分类和结果解读。此外，由于 BRAF 热点 p.V600 与低级别胶质瘤相关，参与者还需对 DNA 甲基化数据得出的拷贝数图谱进行解读，并对其进行 DNA 测序。结果必须在 30 天内返回：结果：技术重现性很高，协调实验室和参与者之间的成对相关性中位数为 0.99（范围 0.94-0.99）。所有中心对基于DNA甲基化的肿瘤分类和拷贝数图谱的解释都是一致的，所有病例的BRAF突变状态都得到了准确报告。12个中心中有11个在30天内成功报告了分析结果：我们的研究表明，12 个国际中心在 DNA 甲基化图谱分析和图谱解读方面具有显著的一致性。这些发现强调了DNA甲基化分析对统一脑肿瘤诊断的潜在贡献。
期刊介绍：
Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.
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