■基因组谱分析的进步导致在髓母细胞瘤(MB)中发现了四个主要的分子亚群,现已纳入世界卫生组织中枢神经系统肿瘤分类。本研究旨在确定马来西亚儿童MB分子亚群的预后意义。
■我们从马来西亚的四个儿科肿瘤中心收集了2003年1月至2017年6月期间18岁以下儿童的MB样本。在德国癌症研究中心使用850kDNA甲基化测试对MB进行分组,海德堡,德国。
■鉴定了来自诊断和治疗为MB的患者的50个样品。50例患者中的2例(4%)肿瘤DNA样本不足以进行分析。在剩下的48名患者中,41(85%)样品被确认为MB,而对于7名(15%)患者,DNA甲基化分类结果与MB的组织病理学诊断有差异,与其他各种诊断。在41例MB患者中,15例患者被分层为标准风险(SR),16例患者为高危(HR),10名婴儿(年龄<3岁)。整个队列的分子分组显示四个(14%)WNT,11(27%)SHH,第3组10(24%),第4组16(39%)。年龄较大的儿童和婴儿的治疗放弃率分别为22.5%和10%,分别。在审查放弃治疗后,对于SR患者,5年无事件生存率(EFS)和总生存率(OS)分别为43.1%±14.7%和46.9±15.6%,分别,在HR,5年EFS和OS均为63.6%±14.5%。婴儿的5年EFS和OS分别为55.6%±16.6%和66.7%±15.7%,分别。WNT肿瘤有最好的5y-OS,在≥3岁的儿童中,其次是第3组,第4组和SHH。在年幼的孩子中,SHHMB患者表现出良好的预后。
■该研究强调了DNA甲基化分析对诊断准确性的重要性。大多数婴儿有SHHMB,他们的EFS和OS与高收入国家报告的相当。由于相对较小的队列和较高的治疗放弃率,关于MB分子亚组的预后意义尚不能得出明确的结论。实施这项高科技研究将有助于病理学家改善诊断并提供MB的分子亚群,允许亚组特异性治疗。
UNASSIGNED: Advancements in genomic profiling led to the discovery of four major molecular subgroups in medulloblastoma (MB), which have now been incorporated into the World Health Organization classification of central nervous system tumors. The current study aimed to determine the prognostic significance of the MB molecular subgroups among children in Malaysia.
UNASSIGNED: We assembled MB samples from children <18 years between January 2003 and June 2017 from four pediatric oncology centers in Malaysia. MB was sub-grouped using 850k DNA methylation testing at German Cancer Research Centre, Heidelberg, Germany.
UNASSIGNED: Fifty samples from patients diagnosed and treated as MB were identified. Two (4%) of the 50 patients\' tumor DNA samples were insufficient for analysis. Of the remaining 48 patients, 41 (85%) samples were confirmed as MB, while for 7 (15%) patients, DNA methylation classification results were discrepant with the histopathological diagnosis of MB, with various other diagnoses. Of the 41 MB patients, 15 patients were stratified as standard-risk (SR), 16 patients as high-risk (HR), and ten as infants (age <3 years old). Molecular subgrouping of the whole cohort revealed four (14%) WNT, 11 (27%) SHH, 10 (24%) Group 3, and 16 (39%) Group 4. Treatment abandonment rates for older children and infants were 22.5% and 10%, respectively. After censoring treatment abandonment, for SR patients, the 5-year event-free survival (EFS) and overall survival (OS) were 43.1% ± 14.7% and 46.9 ± 15.6%, respectively, while in HR, 5-year EFS and OS were both 63.6% ± 14.5%. Infants had a 5-year EFS and OS of 55.6% ± 16.6% and 66.7% ± 15.7%, respectively. WNT tumors had the best 5y-OS, followed by Group 3, Group 4, and SHH in children ≥3 years old. In younger children, SHH MB patients showed favorable outcomes.
UNASSIGNED: The study highlights the importance of DNA methylation profiling for diagnostic accuracy. Most infants had SHH MB, and their EFS and OS were comparable to those reported in high-income countries. Due to the relatively small cohort and the high treatment abandonment rate, definite conclusions cannot be made regarding the prognostic significance of molecular subgroups of MB. Implementing this high-technology investigation would assist pathologists in improving the diagnosis and provide molecular subgrouping of MB, permitting subgroup-specific therapies.