Johnson Mahlon D, Reeder Jay E, O'Connell Mary
Department of Pathology, Division of Neuropathology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14623, USA.
Department of Urology, University of Rochester Medical Center, University of Rochester School of Medicine and Dentistry, Rochester, NY 14623, USA.
Oncol Lett. 2016 Dec;12(6):5344-5348. doi: 10.3892/ol.2016.5377. Epub 2016 Nov 10.
Nucleic acid-editing enzymes of the apolipoprotein B mRNA-editing enzyme (APOBEC) family have been associated with somatic mutation in cancer. However, the role of APOBEC catalytic subunit 3B (APOBEC3B) editing in the pathogenesis of base substitutions in meningiomas is unknown. In the present study, the expression of APOBEC3B was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analyses in five fetal and one adult human leptomeninges and 38 meningiomas. Genomic DNA was sequenced using the Illumina Tru-Seq Cancer Panel. Three meningioma primary cultures were also established and treated with cerebrospinal fluid form patients without neurological disease or platelet-derived growth factor-BB (PDGF-BB), prior to evaluation of APOBEC3B expression. By western blotting, APOBEC3B was revealed to be present in 100% of the fetal leptomeninges, and in 88% of World Health Organization grade I, 100% of grade II and 83% of grade III meningiomas tested, but was not different between grades. RT-qPCR revealed no difference in the mRNA expression of APOBEC3B between grades. Sequencing revealed no elevated levels of the C>T mutations that are characteristic of APOBEC3B editing of genomic DNA. Treatment with cerebrospinal fluid and PDGF-BB had no effect on APOBEC3B protein expression in the leptomeningeal or meningioma cells. These findings suggest that the mutations associated with increased APOBEC3B expression may not be central to the pathogenesis of meningiomas.
载脂蛋白B信使核糖核酸编辑酶(APOBEC)家族的核酸编辑酶与癌症中的体细胞突变有关。然而,APOBEC催化亚基3B(APOBEC3B)编辑在脑膜瘤碱基置换发病机制中的作用尚不清楚。在本研究中,通过逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹分析,检测了5例胎儿和1例成人人类软脑膜组织以及38例脑膜瘤中APOBEC3B的表达。使用Illumina Tru-Seq癌症检测板对基因组DNA进行测序。还建立了3种脑膜瘤原代培养物,在评估APOBEC3B表达之前,用无神经系统疾病患者的脑脊液或血小板衍生生长因子BB(PDGF-BB)进行处理。蛋白质免疫印迹结果显示,APOBEC3B在100%的胎儿软脑膜组织中存在,在检测的世界卫生组织I级脑膜瘤中占88%,II级脑膜瘤中占100%,III级脑膜瘤中占83%,但各分级之间无差异。RT-qPCR结果显示,各分级之间APOBEC3B的mRNA表达无差异。测序结果显示,基因组DNA中具有APOBEC3B编辑特征的C>T突变水平没有升高。用脑脊液和PDGF-BB处理对软脑膜或脑膜瘤细胞中APOBEC3B蛋白表达没有影响。这些发现表明,与APOBEC3B表达增加相关的突变可能不是脑膜瘤发病机制的核心因素。