中枢神经系统(CNS)癌症是成人癌症相关死亡的第10个主要原因,而是儿科患者和年轻人的主要原因。组织学亚型的多样性和复杂性可导致诊断错误。DNA甲基化是一种表观遗传修饰,可提供可用于诊断的肿瘤类型特异性标签。
■我们进行了一项前瞻性研究,使用DNA甲基化分析作为1921年脑肿瘤的主要诊断方法。所有肿瘤都接受了全基因组DNA甲基化的病理诊断和分析,其次是下一代DNA和RNA测序。结果通过DNA甲基化和组织病理学之间的一致性进行分层,建立诊断实用程序。
■在世界卫生组织组织学诊断的1602例病例中,在225例(14%)中,DNA甲基化确定了诊断性错配。78例(5%)没有进行任何分类,在另外110例(7%)中,DNA甲基化证实了诊断并提供了预后信息.在319例携带195种不同的描述性组织学诊断的病例中,DNA甲基化在273例(86%)中提供了明确的诊断,将它们分成55个甲基化类别,并改变了58例(18%)的分级。
■DNA甲基化分析是诊断原发性中枢神经系统肿瘤的可靠方法,提高诊断准确性,减少诊断错误和不确定的诊断,并提供预后子分类。这项研究提供了将DNA甲基化分析作为主要分子诊断测试纳入CNS肿瘤专业指南的框架。好处包括提高诊断准确性,改善患者管理,和临床试验设计的改进。
UNASSIGNED: Central nervous system (CNS) cancer is the 10th leading cause of cancer-associated deaths for adults, but the leading cause in pediatric patients and young adults. The variety and complexity of histologic subtypes can lead to diagnostic errors. DNA methylation is an epigenetic modification that provides a tumor type-specific signature that can be used for diagnosis.
UNASSIGNED: We performed a prospective study using DNA methylation analysis as a primary diagnostic method for 1921 brain tumors. All tumors received a pathology diagnosis and profiling by whole genome DNA methylation, followed by next-generation DNA and RNA sequencing. Results were stratified by concordance between DNA methylation and histopathology, establishing diagnostic utility.
UNASSIGNED: Of the 1602 cases with a World Health Organization histologic diagnosis, DNA methylation identified a diagnostic mismatch in 225 cases (14%), 78 cases (5%) did not classify with any class, and in an additional 110 (7%) cases DNA methylation confirmed the diagnosis and provided prognostic information. Of 319 cases carrying 195 different descriptive histologic diagnoses, DNA methylation provided a definitive diagnosis in 273 (86%) cases, separated them into 55 methylation classes, and changed the grading in 58 (18%) cases.
UNASSIGNED: DNA methylation analysis is a robust method to diagnose primary CNS tumors, improving diagnostic accuracy, decreasing diagnostic errors and inconclusive diagnoses, and providing prognostic subclassification. This study provides a framework for inclusion of DNA methylation profiling as a primary molecular diagnostic test into professional
guidelines for CNS tumors. The benefits include increased diagnostic accuracy, improved patient management, and refinements in clinical trial design.