Department of Neurosurgery, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
FEBS Open Bio. 2012 Jun 1;2:129-34. doi: 10.1016/j.fob.2012.05.004. Print 2012.
Fifty-two samples of pediatric low-grade glioma (48 primary, 4 recurrent) were analyzed for BRAF copy number variation (digital PCR analysis, CopyCaller) and point mutations of BRAF V600E, and exon 5 Q209 in GNAQ, and GNA11, using the MALDI-TOF mass spectrometer with validation by direct sequencing. An increased BRAF copy number was found in 18/47 primary samples tested; 15 of them (83.3%) were pilocytic astrocytomas. A BRAF mutation was found in 3/48 primary tumors, all with a normal BRAF copy number and no GNAQ mutation. One sample had a GNAQ209 mutation (Q209P626) with a normal BRAF gene; none of the tumors had a GNA11Q209 mutation. Recurrent or progressive tumors, analyzed in four patients, had the same molecular genotype as their primary. Increased BRAF copy number and activating BRAF mutations may be involved in the development of low-grade glioma via overactivation of the Ras/Raf pathway. This is the first report of a mutation in GNAQ209 in pediatric low-grade glioma. Understanding the molecular mechanisms underlying glioma initiation and growth may assist in the development of targeted therapies.
52 份小儿低度神经胶质瘤（48 份原发性，4 份复发性）样本经 BRAF 拷贝数变异（数字 PCR 分析，CopyCaller）和 BRAF V600E 点突变、GNAQ 和 GNA11 的外显子 5 Q209 进行了分析，使用 MALDI-TOF 质谱仪进行分析，并通过直接测序进行验证。在 47 个检测的原发性样本中发现 18 个样本的 BRAF 拷贝数增加；其中 15 个（83.3%）为毛细胞型星形细胞瘤。在 48 个原发性肿瘤中发现了 3 个 BRAF 突变，所有这些肿瘤的 BRAF 拷贝数均正常，且无 GNAQ 突变。一个样本有一个 GNAQ209 突变（Q209P626），BRAF 基因正常；所有肿瘤均无 GNA11Q209 突变。对 4 名患者的复发性或进行性肿瘤进行了分析，其分子基因型与其原发性肿瘤相同。BRAF 拷贝数增加和激活的 BRAF 突变可能通过 Ras/Raf 通路的过度激活参与低度神经胶质瘤的发生。这是小儿低度神经胶质瘤中 GNAQ209 突变的首次报道。了解胶质瘤发生和生长的分子机制可能有助于开发靶向治疗。
