Imamura J, Bartram C R, Berthold F, Harms D, Nakamura H, Koeffler H P
University of California, School of Medicine, Los Angeles 90024.
Cancer Res. 1993 Sep 1;53(17):4053-8.
Mutation of the p53 tumor suppressor gene frequently occurs in a variety of tumors including lung, breast, gastrointestinal, and brain, as well as lymphomas-leukemias. Neuroblastoma, one of the most common solid tumors in childhood, often has amplification of the N-myc gene. We examined for mutations of the p53 tumor suppressor gene by single-strand conformational polymorphism using polymerase chain reaction products and direct sequencing method in neuroblastoma; in addition, we assessed the relationship between p53 mutation and N-myc gene amplification in the disease. Of 86 DNA samples from patients with neuroblastoma, two mutations (2%) were found in the coding region of the p53 gene. Each mutation caused a substitution of amino acid residues. One mutation was located in exon 5, and another was in exon 6. N-myc gene was amplified in 26% of the samples. No p53 mutations were found in neuroblastoma samples with N-myc amplification. In the two individuals, p53 mutations appeared as their disease became more progressive. The neurofibromatosis 1 (NF1) gene is frequently abnormal in another neural disorder, neurofibromatosis type 1; in addition, a potential mutational hot spot of NF1 at lysine at codon 1423 has been identified in several types of tumors. Using single-strand conformational polymorphism, we were unable to detect an abnormality in this region of NF1 in 50 samples of neuroblastoma. The data suggest that p53 mutations occasionally are associated with progression of neuroblastomas, and tumorigenetic influences of mutant p53 may differ from those of N-myc.
p53肿瘤抑制基因的突变频繁发生于包括肺癌、乳腺癌、胃肠道癌、脑癌以及淋巴瘤 - 白血病在内的多种肿瘤中。神经母细胞瘤是儿童期最常见的实体瘤之一，常伴有N - myc基因的扩增。我们运用聚合酶链反应产物的单链构象多态性和直接测序法检测神经母细胞瘤中p53肿瘤抑制基因的突变；此外，我们评估了该疾病中p53突变与N - myc基因扩增之间的关系。在86例神经母细胞瘤患者的DNA样本中，在p53基因的编码区发现了两个突变（2%）。每个突变都导致了氨基酸残基的替换。一个突变位于外显子5，另一个位于外显子6。26%的样本中N - myc基因发生了扩增。在N - myc扩增的神经母细胞瘤样本中未发现p53突变。在这两个个体中，随着疾病进展出现了p53突变。神经纤维瘤病1（NF1）基因在另一种神经疾病——1型神经纤维瘤病中经常出现异常；此外，在几种类型的肿瘤中已确定了NF1基因第1423位密码子赖氨酸处的一个潜在突变热点。运用单链构象多态性，我们在50例神经母细胞瘤样本中未能检测到NF1基因该区域的异常。数据表明，p53突变偶尔与神经母细胞瘤的进展相关，并且突变型p53的致瘤影响可能与N - myc不同。
