黄曲霉毒素诱导的第249密码子（R249S）处的TP53突变：暴露、早期检测的生物标志物及治疗靶点。
The aflatoxin-induced TP53 mutation at codon 249 (R249S): biomarker of exposure, early detection and target for therapy.
作者信息
Gouas Doriane, Shi Hong, Hainaut Pierre
机构信息
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France.
出版信息
Cancer Lett. 2009 Dec 1;286(1):29-37. doi: 10.1016/j.canlet.2009.02.057. Epub 2009 Apr 18.
Hepatocellular Carcinoma (HCC) in high-incidence areas (sub-Saharan Africa, South-Eastern Asia) often contains a somatic mutation at codon 249 in TP53 (R249S). This mutation is rare in low-incidence areas of Europe and the United States. There is evidence that R249S occurs as the result of mutagenesis by aflatoxin in a context of HBV chronic infection. Here, we summarize the mechanisms of R249S formation and the possible role of p.R249S protein in HCC pathogenesis. Next, we discuss the significance of R249S as a biomarker to study the natural history of HCC and as a target for therapeutic approaches aimed at restoring wild-type p53 activity.
在肝癌高发地区（撒哈拉以南非洲、东南亚），肝细胞癌（HCC）常常在TP53基因的249密码子处发生体细胞突变（R249S）。这种突变在欧美低发地区较为罕见。有证据表明，R249S突变是在乙肝病毒慢性感染的背景下由黄曲霉毒素诱变所致。在此，我们总结了R249S形成的机制以及p.R249S蛋白在肝癌发病机制中可能发挥的作用。接下来，我们讨论R249S作为研究肝癌自然史的生物标志物以及作为旨在恢复野生型p53活性的治疗方法靶点的意义。
Zotero 插件