AlShail Essam, Alahmari Ahmed Nasser, Dababo Anas A M, Alsagob Maysoon, Al-Hindi Hindi, Khalil Hala, Al Masseri Zainab, AlSalamah Razan, Almohseny Ethar, Alduhaish Amjad, Colak Dilek, Kaya Namik
Department of Neurosciences, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia.
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia.
Front Oncol. 2023 Feb 13;13:1034292. doi: 10.3389/fonc.2023.1034292. eCollection 2023.
Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course. The studies on genetics of PMA are scarce.
In this study, we report one of the largest cohort of pediatric patients with pilomyxoid (PMA) and pilocytic astrocytomas (PA) in Saudi population providing a comprehensive clinical picture, retrospective analysis with long-term follow-up, genome-wide copy number changes, and clinical outcome of these pediatric tumors. We examined and compared genome-wide copy number aberrations (CNAs) and the clinical outcome of the patients with PA and PMA.
The median progression free survival for the whole cohort was 156 months and it was 111 months for the PMA, however, not statistically significantly different between the groups (log-rank test, P = 0.726). We have identified 41 CNAs (34 gains and 7 losses) in all tested patients. Our study yielded the previously reported KIAA1549-BRAF Fusion gene in over 88% of the tested patients (89% and 80% in PMA and PA, respectively). Besides the fusion gene, twelve patients had additional genomic CNAs. Furthermore, pathway and gene network analyses of genes in the fusion region revealed alterations in retinoic acid mediated apoptosis and MAPK signaling pathways and key hub genes that may potentially be involved in tumor growth and progression, including , , , , , , , , and .
Our study is the first report of a large cohort of patients with PMA and PA in the Saudi population that provides detailed clinical features, genomic copy number changes, and outcome of these pediatric tumors and may help better diagnosis and characterization of PMA.
毛细胞型星形细胞瘤（PA）是最常见的儿童脑肿瘤。PA是生长缓慢的肿瘤，生存率高。然而，一种被定义为毛黏液样星形细胞瘤（PMA）的独特肿瘤亚群具有独特的组织学特征，临床病程更具侵袭性。关于PMA遗传学的研究很少。
在本研究中，我们报告了沙特人群中最大的一组儿童毛黏液样（PMA）和毛细胞型星形细胞瘤（PA）患者，提供了全面的临床情况、长期随访的回顾性分析、全基因组拷贝数变化以及这些儿童肿瘤的临床结局。我们检查并比较了PA和PMA患者的全基因组拷贝数畸变（CNA）和临床结局。
整个队列的无进展生存期中位数为156个月，PMA为111个月，然而，两组之间无统计学显著差异（对数秩检验，P = 0.726）。我们在所有测试患者中鉴定出41个CNA（34个增益和7个缺失）。我们的研究在超过88%的测试患者中发现了先前报道的KIAA1549 - BRAF融合基因（PMA和PA中分别为89%和80%）。除了融合基因外，12名患者还有额外的基因组CNA。此外，融合区域基因的通路和基因网络分析揭示了视黄酸介导的凋亡和MAPK信号通路的改变以及可能参与肿瘤生长和进展的关键枢纽基因，包括 ， ， ， ， ， ， ， ，和 。
我们的研究是沙特人群中大量PMA和PA患者的首次报告，提供了这些儿童肿瘤的详细临床特征、基因组拷贝数变化和结局，可能有助于更好地诊断和表征PMA。
