Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen, Calwerstr. 3, 72076, Tuebingen, Germany.
Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University Tuebingen, 72076, Tuebingen, Germany.
J Cancer Res Clin Oncol. 2022 Apr;148(4):857-866. doi: 10.1007/s00432-021-03906-x. Epub 2022 Jan 11.
Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations.
We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases.
368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed.
FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.
低级别胶质瘤（LGG）和混合性神经元-神经胶质肿瘤（MNGT）表现出频繁的 MAPK 通路改变。致癌性成纤维细胞生长因子受体 1（FGFR1）酪氨酸激酶结构域已在各种组织学脑肿瘤中报道。我们旨在确定驱动基因未知的 LGG/MNGT 中 FGFR1 热点突变 N546 和 K656 的频率，并研究 FGFR1 免疫组化作为检测这些改变的潜在工具。
我们分析了 476 例 LGG/MNGT 肿瘤的 KIAA-1549-BRAF 融合、IDH1/2、TERT 启动子、NF1、H3F3A 和其余病例的 FGFR1 突变频率，并在 106 例病例中进行了 FGFR1 免疫组化相关性分析。
476 例 LGG/MNGT 肿瘤中有 368 例存在非 FGFR1 改变。在 108 例其余驱动基因未知的样本中，我们发现了 9 例 FGFR1 p.N546K 和 4 例 FGFR1 p.K656E 突变。其中 5 例为发育不良性神经上皮肿瘤（DNT），4 例为毛细胞星形细胞瘤（PA），3 例为菊形团形成的神经胶质细胞瘤（RGNT）。FGFR1 突变与少突胶质样细胞相关，但与年龄或肿瘤位置无关。在 92 例中观察到 FGFR1 免疫组化表达。PA 和 DNT 中的 FGFR1 免疫反应评分高于弥漫性星形细胞瘤，但未观察到肿瘤中 FGFR1 突变与 FGFR1 表达水平之间的相关性。
FGFR1 热点突变是 LGG/MNGT 中第五种最常见的改变。在驱动基因未知的低级别脑肿瘤中进行 FGFR1 测序分析，可能会产生高达 12%的 FGFR1 N546/K656 突变病例。
