Korshunov Andrey, Meyer Jochen, Capper David, Christians Arne, Remke Marc, Witt Hendrik, Pfister Stefan, von Deimling Andreas, Hartmann Christian
Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, 69120 Heidelberg, Germany.
Acta Neuropathol. 2009 Sep;118(3):401-5. doi: 10.1007/s00401-009-0550-z. Epub 2009 Jun 19.
Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplastic astrocytoma WHO grade III. Recently, genomic aberrations with a high specificity for distinct glioma entities have been described. Pilocytic astrocytomas carry a duplication at chromosome band 7q34 containing a BRAF-KIAA1549 gene fusion in the majority of cases. IDH1 mutations are observed very frequently in adult astrocytomas and IDH2 mutations have been reported in some astrocytomas. We examined a series of 120 astrocytomas including 70 pilocytic astrocytomas WHO grade I and 50 diffuse astrocytomas WHO grade II for both, BRAF-KIAA1549 fusion with a newly developed FISH assay and mutations in IDH1 and IDH2 by direct sequencing. Pilocytic astrocytomas contained the BRAF fusion in 49 cases (70%) but neither IDH1 nor IDH2 mutations. Astrocytomas WHO grade II exhibited IDH1 mutations in 38 cases (76%) but neither IDH2 mutations nor BRAF fusions. Thus, combined molecular analysis of BRAF and IDH1 is a sensitive and highly specific approach to separate pilocytic astrocytoma from diffuse astrocytoma.
毛细胞型星形细胞瘤与弥漫性星形细胞瘤的鉴别诊断常常存在问题，这主要与样本量小有关。由于世界卫生组织（WHO）I级毛细胞型星形细胞瘤、WHO II级弥漫性星形细胞瘤或WHO III级间变性星形细胞瘤的诊断会促使采取不同的治疗策略，因此精确的分类和分级至关重要。最近，已描述了对不同胶质瘤实体具有高特异性的基因组畸变。在大多数情况下，毛细胞型星形细胞瘤在染色体带7q34处存在重复，其中包含BRAF-KIAA1549基因融合。IDH1突变在成人星形细胞瘤中非常常见，并且在一些星形细胞瘤中也报道了IDH2突变。我们通过新开发的荧光原位杂交（FISH）检测法检测了120例星形细胞瘤，其中包括70例WHO I级毛细胞型星形细胞瘤和50例WHO II级弥漫性星形细胞瘤，通过直接测序检测了IDH-1和IDH2的突变。49例（70%）毛细胞型星形细胞瘤含有BRAF融合，但未发现IDH1和IDH2突变。WHO II级星形细胞瘤在38例（76%）中表现出IDH1突变，但未发现IDH2突变和BRAF融合。因此，BRAF和IDH1的联合分子分析是将毛细胞型星形细胞瘤与弥漫性星形细胞瘤区分开来的一种敏感且高度特异的方法。
