Mutation profile of the p53, fhit, p16INK4a/p19ARF and H-ras genes in Indian breast carcinomas.
Mutation profile of the p53, fhit, p16INK4a/p19ARF and H-ras genes in Indian breast carcinomas.
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印度乳腺癌中 p53、fhit、p16INK4a/p19ARF 和 H-ras 基因的突变谱。
DOI：
10.3892/ijo.17.5.1031
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发表时间：
2000
影响因子：
5.2
通讯作者：
G. Shanmugam
中科院分区：
文献类型：
--
作者：
K. Kannan;J. Krishnamurthy;J. Feng;T. Nakajima;N. Tsuchida;G. Shanmugam
乳腺癌是影响印度女性的第二大癌症。癌基因和抑癌基因的遗传改变被归因于乳腺癌的发生。在本研究中，对未经治疗的、非家族性的印度患者的乳腺肿瘤DNA进行了分析，以确定是否存在p53、FHIT、p16INK4a/p19ARF和H-ras基因突变。采用聚合酶链式反应-单链构象多态分析和测序分析方法检测突变情况。用外显子侧翼引物分别扩增和分析p53基因外显子5-8、p16INK4a外显子1-2、p19ARF外显子2、FHIT基因外显子5-9和H-ras基因外显子1-2。P16INK4a/p19ARF和H-ras基因无突变，仅12%有P53突变，8%有FHIT基因突变。肿瘤B18发现两个新的p53基因突变，即第237密码子的ATGright弯曲箭头GTG(Metright弯曲箭头Val)和第263密码子的AATright弯曲箭头Gat(Asnright弯曲箭头Asp)。到目前为止，这两种突变在乳腺癌中都没有报道。肿瘤B20在P53基因第306位密码子上存在无义突变CGA右弯箭TGA(Argright弯箭止点)。在FHIT基因中，肿瘤B1在第8内含子出现TTCT右弯箭头巧妙突变，而在肿瘤B15在第123密码子有一个沉默突变GAG右弯箭头GAA(Gluright弯曲箭头Glu)。我们的结果表明，在所分析的基因中，P53基因在印度乳腺肿瘤中的突变频率高于FHIT、p16INK4a/p19ARF和H-ras基因。FHIT基因的可转录点突变在这些肿瘤中非常罕见。上述基因的突变是互斥的，在FHIT、p16INK4a/p19ARF和H-ras基因中很少发生突变，这表明这些基因在印度乳腺癌中可能不起主要作用。然而，P53基因突变的显著频率表明，P53可能是印度妇女散发性乳腺癌发生的基因之一。
Breast cancer is the second most prevalent cancer affecting Indian women. Genetic alterations of oncogenes and tumor suppressor genes were attributed to the development of breast carcinomas. In the present study, human breast tumor DNAs from untreated, non-familial, Indian patients were analysed for the presence of mutations in p53, fhit, p16INK4a/p19ARF and H-ras genes. Polymerase chain reaction-single strand conformation polymorphism and sequencing analysis were used to detect point mutations. Exons 5-8 of p53, exons 1-2 of p16INK4a, exon 2 of p19ARF, exons 5-9 of fhit gene and exons 1-2 of H-ras genes were amplified and analysed individually using exon-flanking primers. Only 12% of the tumors had mutation in p53, 8% had mutation in fhit gene and none of the tumors showed evidence for mutation in p16INK4a/p19ARF and H-ras genes. Tumor B18 exhibited two novel mutations in the p53 gene, ATGright curved arrow GTG (Metright curved arrow Val) at codon 237 and AATright curved arrow GAT (Asnright curved arrow Asp) at codon 263. Both of these mutations are hitherto unreported in breast carcinomas. Tumor B20 had a non-sense mutation CGAright curved arrow TGA (Argright curved arrow Stop) at codon 306 of p53 gene. In fhit gene, tumor B1 exhibited TTCTright curved arrow TACT mutation at intron 8 and tumor B15 had a silent mutation GAGright curved arrow GAA (Gluright curved arrow Glu) at codon 123. Our results indicate that, among the genes analysed, the p53 gene was more frequently mutated than fhit, p16INK4a/p19ARF and H-ras genes in Indian mammary tumors. Transcribable point mutations of fhit gene were found to be extremely uncommon in these tumors. Mutations in the above genes are mutually exclusive and are infrequent in fhit, p16INK4a/p19ARF and H-ras genes suggesting that these genes may not play a major role in Indian breast carcinomas. However, the significant frequency of mutations in the p53 gene suggest that p53 could be one of the genes involved in the genesis of sporadic breast carcinomas in Indian women.