Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado.
The Morgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, Colorado.
Pediatr Blood Cancer. 2020 Jan;67(1):e28028. doi: 10.1002/pbc.28028. Epub 2019 Oct 8.
The use of next-generation sequencing for fusion identification is being increasingly applied and aids our understanding of tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential for therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated with acute and long-term toxicities. Identification of targetable fusions can shift the treatment paradigm toward earlier integration of molecularly targeted agents.
Patients diagnosed with glial, glioneuronal, and ependymal tumors between 2002 and 2019 were retrospectively reviewed for fusion testing. Testing was done primarily using the ArcherDx FusionPlex Solid Tumor panel, which assesses fusions in 53 genes. In contrast to many previously published series chronicling fusions in pediatric patients, we compared histological features and the tumor classification subtype with the specific fusion identified.
We report 24 cases of glial, glioneuronal, or ependymal tumors from pediatric patients with identified fusions. With the exception of BRAF:KIAA1549 and pilocytic/pilomyxoid astrocytoma morphology, and possibly QKI-MYB and angiocentric glioma, there was not a strong correlation between histological features/tumor subtype and the specific fusion. We report the unusual fusions of PPP1CB-ALK, CIC-LEUTX, FGFR2-KIAA159, and MN1-CXXC5 and detail their morphological features.
Fusion testing proved to be informative in a high percentage of cases. A large majority of fusion events in pediatric glial, glioneuronal, and ependymal tumors can be identified by relatively small gene panels.
下一代测序技术（next-generation sequencing）在融合鉴定中的应用越来越广泛，有助于我们了解肿瘤生物学。一些融合对已批准的靶向药物有反应，而另一些则具有未来的治疗靶向潜力。虽然一些儿科中枢神经系统肿瘤仅通过手术即可治愈，但许多肿瘤需要辅助治疗，这会带来急性和长期毒性。鉴定可靶向的融合可以将治疗模式转向更早地整合分子靶向药物。
回顾性分析了 2002 年至 2019 年间诊断为神经胶质瘤、神经胶质神经元肿瘤和室管膜肿瘤的患者的融合检测情况。检测主要使用 ArcherDx FusionPlex 实体肿瘤panel 进行，该检测panel 评估 53 个基因中的融合。与许多以前发表的系列文章不同，这些文章记录了儿科患者的融合情况，我们将组织学特征和肿瘤分类亚型与鉴定出的特定融合进行了比较。
我们报告了 24 例来自儿科患者的神经胶质瘤、神经胶质神经元肿瘤或室管膜肿瘤，这些患者的肿瘤存在融合。除了 BRAF:KIAA1549 和毛细胞星形细胞瘤/毛细胞黏液样星形细胞瘤形态，以及可能的 QKI-MYB 和血管中心性胶质瘤，组织学特征/肿瘤亚型与特定融合之间没有很强的相关性。我们报告了罕见的 PPP1CB-ALK、CIC-LEUTX、FGFR2-KIAA159 和 MN1-CXXC5 融合，并详细描述了它们的形态学特征。
融合检测在很大比例的病例中提供了有价值的信息。儿科神经胶质瘤、神经胶质神经元肿瘤和室管膜肿瘤中的大多数融合事件可以通过相对较小的基因面板来识别。
