Platten M, Giordano M J, Dirven C M, Gutmann D H, Louis D N
Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital, Boston 02114, USA.
Am J Pathol. 1996 Aug;149(2):621-7.
Pilocytic astrocytomas of the optic nerve (optic nerve gliomas) are closely associated with neurofibromatosis 1 (NF1), and allelic losses of the NF1 gene region on chromosome 17q occur in sporadic pilocytic astrocytomas. We therefore hypothesized that the NF1 gene acts as a tumor suppressor gene in pilocytic astrocytomas, and that NF1 gene expression would be reduced or absent in these tumors. To evaluate this possibility, we examined quantitative and qualitative aspects of NF1 gene expression in six sporadic pilocytic astrocytomas. Surprisingly, the NF1 gene was overexpressed up to fourfold in these tumors when compared with normal brain. This up-regulation was accompanied by immunohistochemical positivity using a carboxyl-terminal antibody and by the absence of mutations in one kilobase of the NF1 coding sequence, consistent with the expressed transcript and protein being full length and probably wild type. Pilocytic astrocytomas showed a marked predominance of transcripts containing exon 23a and lacking exon 9br, the same isoforms that are expressed by normal and reactive astrocytes and malignant astrocytomas. These data illustrate that pilocytic astrocytomas overexpress specific NF1 gene transcripts, perhaps as a regulatory response to growth stimuli. The role of the NF1 gene as a tumor suppressor in pilocytic astrocytomas, however, remains to be proven.
视神经毛细胞型星形细胞瘤（视神经胶质瘤）与1型神经纤维瘤病（NF1）密切相关，散发性毛细胞型星形细胞瘤存在17号染色体长臂上NF1基因区域的等位基因缺失。因此，我们推测NF1基因在毛细胞型星形细胞瘤中作为肿瘤抑制基因发挥作用，且这些肿瘤中NF1基因表达会降低或缺失。为评估这种可能性，我们检测了6例散发性毛细胞型星形细胞瘤中NF1基因表达的定量和定性情况。令人惊讶的是，与正常脑组织相比，这些肿瘤中NF1基因表达上调高达四倍。这种上调伴随着使用羧基末端抗体的免疫组化阳性，且NF1编码序列1千碱基内无突变，这与表达的转录本和蛋白为全长且可能为野生型一致。毛细胞型星形细胞瘤显示含有外显子23a且缺乏外显子9br的转录本占显著优势，这些异构体也由正常和反应性星形胶质细胞以及恶性星形细胞瘤表达。这些数据表明毛细胞型星形细胞瘤过表达特定的NF1基因转录本，可能是作为对生长刺激的一种调节反应。然而，NF1基因在毛细胞型星形细胞瘤中作为肿瘤抑制基因的作用仍有待证实。
