Department of Neurology/Pathology, Oslo University Hospital, Oslo, Norway.
Faculty of Medicine, Institute of Clinical Medicine (KlinMED), University of Oslo, Oslo, Norway.
Pediatr Blood Cancer. 2022 Sep;69(9):e29736. doi: 10.1002/pbc.29736. Epub 2022 May 15.
An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017.
Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification.
We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review.
Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.
在挪威之前发表的关于儿童髓母细胞瘤和幕上原始神经外胚层肿瘤（CNS-PNET）治疗结果的研究中，观察到生存率存在未解释的区域差异。我们现在的目的是重新评估并对所有儿科患者的胚胎性脑肿瘤（不包括非典型畸胎样横纹肌样肿瘤[ATRT]）进行回顾性基于分子的风险分层，这些患者于 2005 年至 2017 年在奥斯陆大学医院接受了手术和治疗。
回顾了所有<20 岁且初始诊断为髓母细胞瘤或 CNS-PNET 的患者的标本。分子分析包括 NanoString 基因表达、分子反转探针分析、Sanger 测序和 850K-甲基化分析。在标准风险非 WNT/非 SHH 髓母细胞瘤中，评估全染色体异常特征以进行分子风险分层。
我们在 53 例非 ATRT 胚胎性肿瘤中发现了 33 例髓母细胞瘤。分子遗传学参数，包括全染色体异常特征，可将 17 例髓母细胞瘤分类为分子高风险。这些患者的 5 年总生存率明显低于其余 16 例髓母细胞瘤患者（52.9%比 87.1%，p=0.036）。我们队列中有 5 例患者的肿瘤被认为是 2021 年中枢神经系统肿瘤分类中的新实体。5 例肿瘤经审查后重新归类为非胚胎性肿瘤。
标准风险非 WNT/非 SHH 髓母细胞瘤的基于分子的风险分层能够更好地识别预后不良的髓母细胞瘤。与其他研究相比，我们的队列显示标准风险非 WNT/非 SHH 髓母细胞瘤中具有分子高风险特征的比例显著增加，这可能导致了之前报告的不良结果数据。
