Jensen S, Paderanga D C, Chen P, Olson K, Edwards M, Iavorone A, Israel M A, Shannon K
Department of Pediatrics, University of California, San Francisco 94143, USA.
Cancer. 1995 Aug 15;76(4):674-7. doi: 10.1002/1097-0142(19950815)76:4<674::aid-cncr2820760421>3.0.co;2-4.
Patients with neurofibromatosis type 1 (NF1) are at increased risk for developing malignant neural crest tumors and juvenile myeloid leukemia. Although the normal allele of the NF1 tumor-suppressor gene is frequently deleted in some of the malignant tumors that arise in patients with NF1, the role of NF1 alterations in the sporadic forms of these cancers is unclear.
A series of intragenic sequence polymorphisms was used to investigate lymphocyte and tumor DNA samples from 22 adults with high grade malignant gliomas for loss of heterozygosity (LOH) at NF1. In addition, an assay based on the polymerase chain reaction was used to screen these tumors for point mutations at codon 1423.
One recurrent anaplastic astrocytoma showed LOH within NF1 but not with a flanking marker located near the gene. Of 21 informative tumors, none showed point mutations affecting codon 1423 of NF1.
These data suggest that LOH at NF1 is uncommon in sporadic high grade astrocytoma, and codon 1423 is not a "hot spot" for activating point mutations in these tumors.
1型神经纤维瘤病（NF1）患者发生恶性神经嵴肿瘤和青少年髓性白血病的风险增加。尽管NF1肿瘤抑制基因的正常等位基因在NF1患者发生的一些恶性肿瘤中经常缺失，但NF1改变在这些癌症散发性形式中的作用尚不清楚。
使用一系列基因内序列多态性来研究22例高级别恶性胶质瘤成年患者的淋巴细胞和肿瘤DNA样本中NF1的杂合性缺失（LOH）。此外，基于聚合酶链反应的检测方法用于筛查这些肿瘤中第1423密码子的点突变。
1例复发性间变性星形细胞瘤显示NF1内存在LOH，但与该基因附近的侧翼标记无关。在21例信息充分的肿瘤中，未发现影响NF1第1423密码子的点突变。
这些数据表明，NF1的LOH在散发性高级别星形细胞瘤中并不常见，并且第1423密码子不是这些肿瘤中激活点突变的“热点”。
