Xu W, Mulligan L M, Ponder M A, Liu L, Smith B A, Mathew C G, Ponder B A
Department of Pathology, University of Cambridge, United Kingdom.
Genes Chromosomes Cancer. 1992 Jun;4(4):337-42. doi: 10.1002/gcc.2870040411.
Type I neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11-12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild-type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild-type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NFI gene may act as a tumour suppressor.
I型神经纤维瘤病（NF1）是一种常见的常染色体显性疾病，可影响源自神经嵴的组织。其表现多样，包括生长发育的全身性紊乱以及良性和恶性肿瘤（包括嗜铬细胞瘤和神经纤维肉瘤）风险的增加。NF1基因座已被定位到17q11 - 12染色体带，最近NF1基因已被克隆。在一些患者的体质基因型中发现的缺失表明，NF1表型可能源于NF1基因的功能丧失突变，这与它是一种肿瘤抑制基因的假设一致。然而，迄今为止，对NF1肿瘤的分析尚未发现包含NF1基因座的频繁等位基因缺失，即野生型NF1等位基因的缺失，而这将支持该假设。我们报告了7例NF1嗜铬细胞瘤中每一例NF1区域侧翼标记的等位基因缺失情况。在可确定此情况的3个肿瘤中的每一个中，缺失均涉及野生型染色体。这些结果提供了强有力的证据，表明至少在肾上腺髓质细胞中，NFI基因可能作为一种肿瘤抑制基因发挥作用。
