Hosoi G, Hara J, Okamura T, Osugi Y, Ishihara S, Fukuzawa M, Okada A, Okada S, Tawa A
Department of Pediatrics, Osaka University Hospital, Japan.
Cancer. 1994 Jun 15;73(12):3087-93. doi: 10.1002/1097-0142(19940615)73:12<3087::aid-cncr2820731230>3.0.co;2-9.
The p53 gene frequently is affected by point mutations, rearrangements, or deletions that contribute to the genesis or progression of a wide variety of human adult solid tumors; however, to the authors' knowledge, this gene alteration has not been analyzed in neuroblastoma.
Genomic DNA samples from 20 children with neuroblastoma, including 16 patients with advanced disease, were screened for the presence of mutations in exons 5-9 of the p53 gene, where over 90% of mutations have been reported to be located in human cancer. The screening technique employed polymerase chain reaction/single-strand conformation polymorphism analysis followed by direct DNA sequencing.
Heterozygous mutations were detected in 2 of the 20 cases. A silent mutation (T to G transversion) at codon 172 and a missense mutation (G to T transversion) at codon 259 were found in patients with Stage II and Stage IV disease, respectively. Thus, p53 mutations were found to occur in neuroblastoma, but at a low frequency (2 of 20).
Our data suggest that in a minority of neuroblastomas, p53 gene mutations may play a contributing role in tumorigenesis, but other genes presumably play a major role in this tumor.
p53基因经常受到点突变、重排或缺失的影响，这些变化会导致多种人类成人实体瘤的发生或进展；然而，据作者所知，尚未在神经母细胞瘤中分析这种基因改变。
对20例神经母细胞瘤患儿的基因组DNA样本进行筛查，其中包括16例晚期疾病患者，检测p53基因外显子5-9中是否存在突变，据报道，超过90%的人类癌症突变位于该区域。筛查技术采用聚合酶链反应/单链构象多态性分析，随后进行直接DNA测序。
20例中有2例检测到杂合突变。分别在II期和IV期疾病患者中发现密码子172处的沉默突变（T到G颠换）和密码子259处的错义突变（G到T颠换）。因此，发现p53突变在神经母细胞瘤中出现，但频率较低（20例中有2例）。
我们的数据表明，在少数神经母细胞瘤中，p53基因突变可能在肿瘤发生中起一定作用，但其他基因可能在这种肿瘤中起主要作用。
