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Molecular profiling of pediatric and adolescent ependymomas: identification of genetic variants using a next-generation sequencing panel
Journal of Neuro-Oncology ( IF 3.9 ) Pub Date : 2021-09-27 , DOI: 10.1007/s11060-021-03848-x
Débora Cabral de Carvalho Corrêa 1, 2 , Francine Tesser-Gamba 1 , Indhira Dias Oliveira 1 , Nasjla Saba da Silva 1 , Andrea Maria Capellano 1 , Maria Teresa de Seixas Alves 1, 3 , Frederico Adolfo Benevides Silva 1, 4 , Patrícia Alessandra Dastoli 1, 5 , Sergio Cavalheiro 1, 5 , Silvia Regina Caminada de Toledo 1, 2, 6
Affiliation  

Purpose

Ependymoma (EPN) accounts for approximately 10% of all primary central nervous system (CNS) tumors in children and in most cases, chemotherapy is ineffective and treatment remains challenging. We investigated molecular alterations, with a potential prognostic marker and therapeutic target in EPNs of childhood and adolescence, using a next-generation sequencing (NGS) panel specific for pediatric neoplasms.

Methods

We selected 61 samples with initial diagnosis of EPN from patients treated at Pediatric Oncology Institute-GRAACC/UNIFESP. All samples were divided according to the anatomical compartment of the CNS - 42 posterior fossa (PF), 14 supratentorial (ST), and five spinal (SP). NGS was performed to identify somatic genetic variants in tumor samples using the Oncomine Childhood Cancer Research Assay® (OCCRA®) panel, from Thermo Fisher Scientific®.

Results

Genetic variants were identified in 24 of 61 (39.3%) tumors and over 90% of all variants were pathogenic or likely pathogenic. The most commonly variants detected were in CIC, ASXL1, and JAK2 genes and have not been reported in EPN yet. MN1-BEND2 fusion, alteration recently described in a new CNS tumor type, was identified in one ST sample that was reclassified as astroblastoma. Additionally, YAP1‐MAMLD1 fusion, a rare event associated with good outcome in ST-EPN, was observed in two patients diagnosed under 2 years old.

Conclusions

Molecular profiling by the OCCRA® panel showed novel alterations in pediatric and adolescent EPNs, which highlights the clinical importance in identifying genetic variants for patients’ prognosis and therapeutic orientation.



中文翻译:

儿科和青少年室管膜瘤的分子谱分析:使用下一代测序面板鉴定遗传变异

目的

室管膜瘤 (EPN) 约占儿童所有原发性中枢神经系统 (CNS) 肿瘤的 10%,在大多数情况下,化疗无效,治疗仍然具有挑战性。我们使用专门针对儿科肿瘤的下一代测序 (NGS) 小组研究了分子改变,以及儿童和青春期 EPNs 中潜在的预后标志物和治疗靶点。

方法

我们从儿科肿瘤研究所-GRAACC/UNIFESP 接受治疗的患者中选择了 61 个初步诊断为 EPN 的样本。所有样本均根据 CNS 的解剖隔室进行划分 - 42 个后颅窝 (PF)、14 个幕上 (ST) 和 5 个脊柱 (SP)。使用来自 Thermo Fisher Scientific® 的 Oncomine Childhood Cancer Research Assay® (OCCRA®) 面板进行 NGS 以鉴定肿瘤样本中的体细胞遗传变异。

结果

在 61 个 (39.3%) 肿瘤中的 24 个(39.3%)中发现了遗传变异,超过 90% 的变异是致病性的或可能是致病性的。检测到的最常见变异是在CICASXL1JAK2基因中,尚未在 EPN 中报道。MN1-BEND2融合是最近在一种新的 CNS 肿瘤类型中描述的改变,在一个被重新分类为星形母细胞瘤的 ST 样本中发现。此外,在两名诊断为 2 岁以下的患者中观察到YAP1-MAMLD1融合,这是一种与 ST-EPN 良好结果相关的罕见事件。

结论

OCCRA® 小组的分子谱分析显示了儿科和青少年 EPN 的新变化,这突出了在识别基因变异对患者预后和治疗方向方面的临床重要性。

更新日期:2021-09-29
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