MUTATIONS IN P53 AS POTENTIAL MOLECULAR MARKERS FOR HUMAN BREAST-CANCER
MUTATIONS IN P53 AS POTENTIAL MOLECULAR MARKERS FOR HUMAN BREAST-CANCER
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DOI：
10.1073/pnas.88.23.10657
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
SUKUMAR, S
中科院分区：
文献类型：
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作者：
RUNNEBAUM, IB;NAGARAJAN, M;SUKUMAR, S
基于人类乳腺肿瘤中p53基因位点附近染色体17 p位点杂合性丢失的高发生率，我们研究了乳腺肿瘤中p53肿瘤抑制基因突变的频率和影响。我们检测了20个乳腺癌细胞系和59个原发性乳腺肿瘤中的p53基因。北方印迹分析、免疫沉淀和核苷酸测序分析显示，在50%的测试细胞系中存在异常mRNA表达、蛋白质过度表达和p53基因点突变。开发了多重PCR测定法来搜索p53基因组位点中的缺失。基因组DNA的多重PCR显示，高达36%的原发性肿瘤在p53位点含有畸变。单链构象多态性分析发现59例原发性肿瘤中有10例（17%）p53基因外显子5-9突变。我们的结论是，与HER 2/NEU，MYC或INT 2癌基因位点扩增相比，p53基因突变和缺失是乳腺癌中最常见的与单个基因相关的遗传变化。p53基因突变与疾病状态相关，可作为乳腺癌诊断和/或预后的一个有价值的标志物。
Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors, we investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. We examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell lines tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. Multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.