We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease.

中文翻译：

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BRAF V600E突变介导年轻多态性低度神经上皮肿瘤的FDG-蛋氨酸摄取失配。

我们介绍了一个与肿瘤相关的难治性癫痫的14岁男孩的病例。正电子发射断层扫描成像显示肿瘤内11C-蛋氨酸摄取异质性高，18F-氟代脱氧葡萄糖摄取异质性低。组织病理学和基因组学分析证实该肿瘤为BRAF V600E突变的年轻多态性低级神经上皮性肿瘤（PLNTY）。在高蛋氨酸摄取区域，我们观察到蛋氨酸的主要转运蛋白L型氨基酸转运蛋白1（LAT1）的蛋白质水平增加；c-Myc; 和丝裂原活化蛋白激酶（MAPK）途径的组成。我们还发现，LAT1表达与BRAF V600E突变以及随后的MAPK信号传导和c-Myc激活有关。MAPK途径的药理和遗传抑制作用可抑制BRAF V600E突变的PLNTY和胶质母细胞瘤细胞中c-Myc和LAT1的表达。BRAF抑制剂dabrafenib适度抑制PLNTY中的细胞活力。总体而言，我们的结果表明，BRAF V600E突变激活的MAPK信号传导和下游c-Myc诱导了PLNTY中特定的代谢改变，并且可能代表该疾病的治疗目标。