Grob Sydney T, Nobre Liana, Campbell Kristen R, Davies Kurtis D, Ryall Scott, Aisner Dara L, Hoffman Lindsey, Zahedi Shadi, Morin Andrew, Crespo Michele, Nellan Anandani, Green Adam L, Foreman Nicholas, Vibhakar Rajeev, Hankinson Todd C, Handler Michael H, Hawkins Cynthia, Tabori Uri, Kleinschmidt-DeMasters B K, Mulcahy Levy Jean M
Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA.
The Morgan Adams Foundation Pediatric Brain Tumor Research Program, Children's Hospital Colorado, Aurora, Colorado, USA.
Neurooncol Adv. 2020 Aug 24;2(1):vdaa103. doi: 10.1093/noajnl/vdaa103. eCollection 2020 Jan-Dec.
The mitogen-activated protein kinases/extracelluar signal-regulated kinases pathway is involved in cell growth and proliferation, and mutations in have made it an oncogene of interest in pediatric cancer. Previous studies found that mutations as well as fusions are common in intracranial low-grade gliomas (LGGs). Fewer studies have tested for the presence of these genetic changes in spinal LGGs. The aim of this study was to better understand the prevalence of BRAF and other genetic aberrations in spinal LGG.
We retrospectively analyzed 46 spinal gliomas from patients aged 1-25 years from Children's Hospital Colorado (CHCO) and The Hospital for Sick Children (SickKids). CHCO utilized a 67-gene panel that assessed and additionally screened for other possible genetic abnormalities of interest. At SickKids, was assessed by droplet digital polymerase chain reaction and immunohistochemistry. BRAF fusions were detected by fluorescence in situ hybridization, reverse transcription polymerase chain reaction, or NanoString platform. Data were correlated with clinical information.
Of 31 samples with complete fusion analysis, 13 (42%) harbored . All 13 (100%) patients with confirmed survived the entirety of the study period (median [interquartile range] follow-up time: 47 months [27-85 months]) and 15 (83.3%) fusion-negative patients survived (follow-up time: 37.5 months [19.8-69.5 months]). Other mutations of interest were also identified in this patient cohort including , , , , , and deletion.
was seen in higher frequency than or other genetic aberrations in pediatric spinal LGGs and experienced lower death rates compared to negative patients, although this was not statistically significant.
丝裂原活化蛋白激酶/细胞外信号调节激酶通路参与细胞生长和增殖，该通路中的突变使其成为小儿癌症中一个备受关注的癌基因。先前的研究发现，该突变以及融合在颅内低级别胶质瘤（LGGs）中很常见。较少有研究检测脊髓LGGs中这些基因变化的存在情况。本研究的目的是更好地了解脊髓LGG中BRAF及其他基因畸变的发生率。
我们回顾性分析了来自科罗拉多儿童医院（CHCO）和病童医院（SickKids）的1至25岁患者的46例脊髓胶质瘤。CHCO使用了一个67基因panel，该panel评估了并额外筛查了其他可能感兴趣的基因异常。在SickKids，通过液滴数字聚合酶链反应和免疫组织化学评估。通过荧光原位杂交、逆转录聚合酶链反应或NanoString平台检测BRAF融合。数据与临床信息相关联。
在31例进行了完整融合分析的样本中，13例（42%）存在。所有13例确诊的患者在整个研究期间均存活（中位[四分位间距]随访时间：47个月[27 - 85个月]），15例（83.3%）融合阴性患者存活（随访时间：37.5个月[19.8 - 69.5个月]）。在该患者队列中还鉴定出了其他感兴趣的突变，包括、、、、、和缺失。
在小儿脊髓LGGs中，的出现频率高于或其他基因畸变，与阴性患者相比死亡率较低，尽管这在统计学上不显著。
