BACKGROUND Molecular signatures are being increasingly incorporated into cancer classification systems. DNA methylation-based central nervous system (CNS) tumor classification is being recognized as having the potential to aid in cases of difficult histopathological diagnoses. Here, we present our institutional clinical experience in integrating a DNA-methylation-based classifier into clinical practice and report its impact on CNS tumor patient diagnosis and treatment. METHODS Prospective case review was undertaken at CNS tumor board discussions over a 3-year period and 55 tumors with a diagnosis that was not certain to two senior neuropathologists were recommended for methylation profiling based on diagnostic needs. Tumor classification, calibrated scores, and copy number variant (CNV) plots were obtained for all 55 cases. These results were integrated with histopathological findings to reach a final diagnosis. We retrospectively reviewed each patient's clinical course to determine final neuro-pathology diagnoses and the impact of methylation profiling on their clinical management, with a focus on changes that were made to treatment decisions. RESULTS Following methylation profiling, 46 of the 55 (84%) challenging cases received a clinically relevant diagnostic alteration, with two-thirds having a change in the histopathological diagnosis and the other one-third obtaining clinically important molecular diagnostic or subtyping alterations. WHO grading changed by 27% with two-thirds receiving a higher grade. Patient care was directly changed in 15% of all cases with major changes in clinical decision-making being made for these patients to avoid unnecessary or insufficient treatment. CONCLUSIONS The integration of methylation-based CNS tumor classification into diagnostics has a substantial clinical benefit for patients with challenging CNS tumors while also avoiding unnecessary health care costs. The clinical impact shown here may prompt the expanded use of DNA methylation profiling for CNS tumor diagnostics within prominent neuro-oncology centers globally.

中文翻译：

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中枢神经系统肿瘤甲基化分类器改变了神经肿瘤学的实践方法，对脑肿瘤的诊断提出了挑战，并直接影响到患者的护理。

背景技术分子标记越来越多地并入癌症分类系统中。基于DNA甲基化的中枢神经系统（CNS）肿瘤分类被认为具有在组织病理学诊断困难的情况下提供帮助的潜力。在这里，我们介绍了将基于DNA甲基化的分类器整合到临床实践中的机构临床经验，并报告了其对中枢神经系统肿瘤患者诊断和治疗的影响。方法在为期3年的中枢神经系统肿瘤委员会讨论中，进行了前瞻性病例回顾，根据诊断需要，推荐了55位诊断不确定的肿瘤，建议两位资深神经病理学家进行甲基化分析。获得了全部55例患者的肿瘤分类，校准评分和拷贝数变异（CNV）图。将这些结果与组织病理学发现相结合，以进行最终诊断。我们回顾性地回顾了每位患者的临床病历，以确定最终的神经病理学诊断以及甲基化分析对他们临床管理的影响，重点是对治疗决策的改变。结果在进行甲基化分析后，在55例具有挑战性的病例中，有46例（占84％）进行了临床相关的诊断改变，其中三分之二的患者在组织病理学诊断上发生了改变，另外三分之一在临床上具有重要的分子诊断或亚型改变。世卫组织等级改变了27％，其中三分之二获得了更高的等级。在所有病例中，有15％直接改变了患者的护理方式，为避免不必要或不足的治疗，对这些患者的临床决策做出了重大改变。结论将基于甲基化的CNS肿瘤分类整合到诊断程序中对于具有挑战性的CNS肿瘤患者具有重大的临床益处，同时还避免了不必要的医疗保健费用。此处显示的临床影响可能会促使DNA甲基化图谱在全球知名神经肿瘤学中心广泛用于CNS肿瘤诊断。