Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification.
Mutation of the p53 gene in neuroblastoma and its relationship with N-myc amplification.
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发表时间：
1993-09
期刊：
影响因子：
11.2
通讯作者：
Jun Imamura;Claus R. Bartram;Frank Berthold;Dieter Harms;Haruhiko Nakamura;H. Koeffler
中科院分区：
文献类型：
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作者：
Jun Imamura;Claus R. Bartram;Frank Berthold;Dieter Harms;Haruhiko Nakamura;H. Koeffler
P53抑癌基因的突变经常发生在各种肿瘤中，包括肺癌、乳腺癌、胃肠道肿瘤和脑肿瘤，以及淋巴瘤-白血病。神经母细胞瘤是儿童最常见的实体瘤之一，常伴有N-myc基因扩增。我们采用单链构象多态技术，采用聚合酶链式反应产物直接测序法，检测了神经母细胞瘤中抑癌基因P53的突变情况，并探讨了P53突变与N-myc基因扩增的关系。在86例神经母细胞瘤患者的DNA样本中，发现P53基因编码区有2个突变(2%)。每个突变都会导致氨基酸残基的替换。1个突变位于第5外显子，1个突变位于第6外显子，26%的标本扩增出N-myc基因。在N-myc扩增的神经母细胞瘤标本中未发现P53突变。在这两个人中，随着疾病的进展，出现了p53突变。神经纤维瘤病1(NF1)基因在另一种神经疾病-神经纤维瘤病1型中经常异常；此外，在几种类型的肿瘤中发现了NF1在1423位赖氨酸的潜在突变热点。利用单链构象多态技术，我们未能在50例神经母细胞瘤样本中检测到NF1这一区域的异常。这些数据表明，P53突变偶尔与神经母细胞瘤的进展有关，突变型P53对肿瘤发生的影响可能不同于N-myc。
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.