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中国肝细胞癌中p53基因的畸变

Aberrations of p53 gene in human hepatocellular carcinoma from China.

作者信息

Li D, Cao Y, He L, Wang N J, Gu J R

机构信息

National Laboratory for Oncogenes and Related Genes, Shanghai Cancer Institute, Peoples Republic of China.

出版信息

Carcinogenesis. 1993 Feb;14(2):169-73. doi: 10.1093/carcin/14.2.169.

Abstract

Allele losses and mutations have been examined in 38 cases of primary hepatocellular carcinomas (HCC) from different geographic areas of China by Southern, single-strand conformational polymorphism (SSCP) and direct DNA sequencing analyses. Two of 12 samples from Qi-Dong and six of 18 HCCs from Shanghai showed loss of heterozygosity (LOH) at the loci on chromosome 17p13.3. All of the nine mutations in the p53 gene detected in HCC from Qi-Dong were clustered at the third base of codon 249, i.e. G:C to T:A, leading to an arginine to serine change. In contrast, 18 HCC samples from Shanghai contained three mutations at codons 249, 255 and 279. These results suggested a relationship between the spectrum of p53 aberration and environmental risk factors in these two geographic areas. Since no correlation between the state of HBV DNA and p53 aberration was observed, other factors such as dietary exposure to aflatoxin B1 (AFB1) might be responsible for the mutational hotspot at codon 249 in HCCs from Qi-Dong area.

摘要

通过Southern杂交、单链构象多态性(SSCP)分析及直接DNA测序分析,对来自中国不同地理区域的38例原发性肝细胞癌(HCC)进行了等位基因缺失和突变检测。启东的12份样本中有2份、上海的18例HCC中有6例在17号染色体p13.3位点出现杂合性缺失(LOH)。在启东HCC中检测到的9个p53基因突变均聚集在第249密码子的第3位碱基,即从G:C突变为T:A,导致精氨酸变为丝氨酸。相比之下,上海的18份HCC样本在第249、255和279密码子处有3个突变。这些结果表明这两个地理区域p53基因异常谱与环境危险因素之间存在关联。由于未观察到HBV DNA状态与p53基因异常之间的相关性,其他因素如饮食中黄曲霉毒素B1(AFB1)暴露可能是启东地区HCC第249密码子突变热点的原因。

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