ABSTRACT

In the clinical management of paediatric solid tumours, histological examination of tumour tissue obtained by a biopsy remains the gold standard to establish a conclusive pathological diagnosis. The DNA methylation pattern of a tumour is known to correlate with the histopathological diagnosis across cancer types and is showing promise in the diagnostic workup of tumour samples. This methylation pattern can be detected in the cell-free DNA. Here, we provide proof-of-concept of histopathologic classification of paediatric tumours using cell-free reduced representation bisulphite sequencing (cf-RRBS) from retrospectively collected plasma and cerebrospinal fluid samples. We determined the correct tumour type in 49 out of 60 (81.6%) samples starting from minute amounts (less than 10 ng) of cell-free DNA. We demonstrate that the majority of misclassifications were associated with sample quality and not with the extent of disease. Our approach has the potential to help tackle some of the remaining diagnostic challenges in paediatric oncology in a cost-effective and minimally invasive manner.

摘要

在儿科实体瘤的临床管理中，通过活检获得的肿瘤组织的组织学检查仍然是建立结论性病理诊断的金标准。已知肿瘤的 DNA 甲基化模式与癌症类型的组织病理学诊断相关，并且在肿瘤样本的诊断检查中显示出前景。这种甲基化模式可以在无细胞 DNA 中检测到。在这里，我们使用回顾性收集的血浆和脑脊液样本的无细胞还原代表性亚硫酸氢盐测序 (cf-RRBS) 提供儿科肿瘤组织病理学分类的概念验证。我们从微量（少于 10 ng）无细胞 DNA 开始，在 60 个样本中的 49 个（81.6%）样本中确定了正确的肿瘤类型。我们证明大多数错误分类与样本质量有关，而不是与疾病程度有关。我们的方法有可能以具有成本效益和微创的方式帮助解决儿科肿瘤学中剩余的一些诊断挑战。