A novel germ-line mutation in the noncoding region of the p53 gene in a Li-Fraumeni family
A novel germ-line mutation in the noncoding region of the p53 gene in a Li-Fraumeni family
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DOI：
10.1016/s0165-4608(97)00258-6
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发表时间：
1998-05-01
影响因子：
--
通讯作者：
Zaizov, R
中科院分区：
文献类型：
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作者：
Barel, D;Avigad, S;Zaizov, R
我们确定了一个新的生殖系p53突变的非编码，非剪接区的李Fraumeni家庭。属于该家族的患者包括儿童髓母细胞瘤和横纹肌肉瘤患者以及乳腺癌患者。对p53基因的3个位点进行杂合性缺失（洛）分析。其中一个位点保持杂合性，而其他两个位点表现为洛合性缺失。第三个基因座的序列分析鉴定了外显子6下游63 bp的5 '-CCGGGTGA-3'到5 '-CCAGGTTGGA-3'的变化。在两名儿童患者的生殖系和每个相关的父母中鉴定出突变。我们排除了p53基因整个编码区的任何额外突变，包括剪接位点内含子序列。在正常和肿瘤石蜡包埋组织中均检测到p53蛋白的强阳性核染色。85名正常人对这种改变呈阴性，因此支持它是一种突变。这些结果可能表明，p53基因的非编码区内的遗传变化可能作为激活该基因的另一种机制。该基因非编码区的突变应进一步研究。(C)Elsevier Science Inc.，1998.
We identified a novel germ-line p53 mutation in the noncoding, nonsplicing regions of a Li-Fraumeni family. Patients belonging to this family included pediatric medulloblastoma and rhabdomyosarcoma patients and a breast carcinoma patient. Three positions in the p53 gene were analyzed for loss of heterozygosity (LOH). One of the three loci retained heterozygosity, whereas the other two exhibited LOH. Sequence analysis of the third locus identified a change of 5'-CCGGGTGA-3' to 5'-CCAGGTTGGA-3', 63 bp downstream of exon 6. The mutation was identified in the germ line of the two pediatric patients and in each of the related parents. We excluded any additional mutation in the entire coding region of the p53 gene, including splice-site intronic sequences. Strong positive nuclear staining of the p53 protein was detected in both normal and tumor paraffin-embedded tissues. Eighty five normal persons were negative for this alteration, which thus supports it as a mutation. These results may indicate that genetic changes within the noncoding region of the p53 gene may serve as an alternative mechanism of activating this gene. Mutations in the noncoding region of this gene should be further studied. (C) Elsevier Science Inc., 1998.