Abstract：
OBJECTIVE: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort.
METHODS: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist.
RESULTS: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients.
CONCLUSIONS: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
METHODS: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist.
RESULTS: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients.
CONCLUSIONS: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
摘要：
小儿脑瘤很少见，建立精确的诊断可能是具有挑战性的。DNA甲基化谱的分析已被证明是对中枢神经系统（CNS）肿瘤进行高精度分类的可靠方法。我们旨在前瞻性分析在瑞典诊断的中枢神经系统肿瘤，评估在未经选择的队列中，将基于DNA甲基化的分类添加到标准儿科脑肿瘤诊断中的临床影响。
只要有足够的肿瘤材料，在2017-2020年期间在儿童（0-18岁）中诊断出的所有中枢神经系统肿瘤都有资格纳入。使用全基因组DNA甲基化谱分析分析肿瘤，并通过MNP脑肿瘤分类器进行分类。将最初的组织病理学诊断与基于DNA甲基化的分类进行比较。对于不一致的结果，由经验丰富的神经病理学家进行盲法再评估.
分析了240例基于组织病理学诊断的肿瘤。在78%的病例中达到0.84或更高的高置信度甲基化评分。在69%中，组织病理学诊断得到证实，对于其中一些也精致的，6%不一致，重新评估有利于基于甲基化的分类。在剩下的3%的案例中，甲基化类型为非贡献型.诊断的变化将对所有患者中5％的临床管理产生直接影响。
将基于DNA甲基化的肿瘤分类整合到常规临床分析中可以改善诊断，并提供对治疗决策重要的分子信息。甲基化分析的结果应在临床和组织病理学信息的背景下解释。
只要有足够的肿瘤材料，在2017-2020年期间在儿童（0-18岁）中诊断出的所有中枢神经系统肿瘤都有资格纳入。使用全基因组DNA甲基化谱分析分析肿瘤，并通过MNP脑肿瘤分类器进行分类。将最初的组织病理学诊断与基于DNA甲基化的分类进行比较。对于不一致的结果，由经验丰富的神经病理学家进行盲法再评估.
分析了240例基于组织病理学诊断的肿瘤。在78%的病例中达到0.84或更高的高置信度甲基化评分。在69%中，组织病理学诊断得到证实，对于其中一些也精致的，6%不一致，重新评估有利于基于甲基化的分类。在剩下的3%的案例中，甲基化类型为非贡献型.诊断的变化将对所有患者中5％的临床管理产生直接影响。
将基于DNA甲基化的肿瘤分类整合到常规临床分析中可以改善诊断，并提供对治疗决策重要的分子信息。甲基化分析的结果应在临床和组织病理学信息的背景下解释。
