Rajagopal Revathi, Teng Ay Jiuan, Jawin Vida, Wong Oy Leng, Mahsin Hakimah, Abd Rani Nor Haizura, Yap Tsiao Yi, Gunasagaran Kogilavani, Thevarajah Asohan, Yeoh Seoh Leng, Ong Gek Bee, Ariffin Hany, Jones David, Bouffet Eric, Gottardo Nicholas G
Division of Hematology, Oncology and Bone Marrow Transplantation, Department of Pediatrics, University Malaya Medical Center, Kuala Lumpur, Malaysia.
Division of Hematology and Oncology, Department of Pediatrics, Sarawak General Hospital, Ministry of Health Malaysia, Kuching, Malaysia.
Front Oncol. 2023 Oct 18;13:1278611. doi: 10.3389/fonc.2023.1278611. eCollection 2023.
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.
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.
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.
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.
基因组分析技术的进步促使人们发现了髓母细胞瘤（MB）的四个主要分子亚组，目前这些亚组已被纳入世界卫生组织中枢神经系统肿瘤分类中。本研究旨在确定马来西亚儿童MB分子亚组的预后意义。
我们收集了2003年1月至2017年6月期间来自马来西亚四个儿科肿瘤中心的18岁以下儿童的MB样本。在德国海德堡的德国癌症研究中心使用850k DNA甲基化检测对MB进行亚组分类。
共鉴定出50例诊断和治疗为MB的患者样本。50例患者的肿瘤DNA样本中有2例（4%）不足以进行分析。在其余48例患者中，41例（85%）样本被确认为MB，而7例（15%）患者的DNA甲基化分类结果与MB的组织病理学诊断不一致，有各种其他诊断。在41例MB患者中，15例被分层为标准风险（SR），16例为高风险（HR），10例为婴儿（年龄<3岁）。整个队列的分子亚组分析显示，有4例（14%）WNT亚组、11例（27%）SHH亚组、10例（24%）第3组和16例（39%）第4组。大龄儿童和婴儿的治疗放弃率分别为22.5%和10%。在剔除治疗放弃病例后，SR患者的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%，而HR患者的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%±1 ,5.7%。在≥3岁的儿童中，WNT肿瘤的5年总生存率最佳，其次是第3组、第4组和SHH亚组。在年幼患儿中，SHH MB患者显示出良好的预后。
该研究强调了DNA甲基化分析对诊断准确性的重要性。大多数婴儿患有SHH MB，其EFS和OS与高收入国家报道的相当。由于队列相对较小且治疗放弃率较高，关于MB分子亚组的预后意义无法得出明确结论。开展这项高科技研究将有助于病理学家提高诊断水平，并提供MB的分子亚组分类，从而实现亚组特异性治疗。
