Murgia A, Anglani F, Vinanzi C, Polli R, Basso G, Perilongo G, Giangaspero F, Zacchello F
Department of Paediatrics, University of Padua, Italy.
Eur J Cancer. 1998 Mar;34(4):577-9. doi: 10.1016/s0959-8049(97)10078-8.
We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region in tumours of neuroepithelial tissues, where the activity of neurofibromin seems to be crucial in regulating the mechanisms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were identified in the tumours analysed. We conclude that the loss of NF1 gene tumour suppressor function, that might lead or contribute to the development of malignancies in neuroectodermal tissues, is not due to structural abnormalities of the region of the gene which interacts with p21 ras.
我们对1型神经纤维瘤病（NF1）基因最保守区域——鸟嘌呤三磷酸酶（GTPase）激活蛋白（GAP）相关结构域（NF1 GRD）进行了突变分析，肿瘤抑制功能归因于该结构域。分析了60例原发性神经外胚层肿瘤。该研究的理论依据是，在神经上皮组织肿瘤中有可能发现导致该区域功能丧失的结构改变，在这些肿瘤中，神经纤维瘤蛋白的活性似乎在调节由p21 ras介导的信号转导和细胞转化机制中至关重要。在对整个NF1 GRD序列进行分析后，在所分析的肿瘤中未发现突变。我们得出结论，NF1基因肿瘤抑制功能的丧失可能导致或促成神经外胚层组织恶性肿瘤的发生，这并非由于该基因与p21 ras相互作用区域的结构异常所致。
