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首页> 外文期刊>World Journal of Gastroenterology >Codon 249 mutation in exon 7 of p53 gene in plasma DNA: maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area, China
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Codon 249 mutation in exon 7 of p53 gene in plasma DNA: maybe a new early diagnostic marker of hepatocellular carcinoma in Qidong risk area, China

机译：血浆DNA p53基因第7外显子的249位密码子突变：可能是启东危险地区肝细胞癌的早期诊断新指标

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AIM: One of the characteristics of hepatocellular carcinoma (HCC) in Qidong area is the selective mutation resulting in a serine substitution at codon 249 of the p53 gene (1, 20), and it has been identified as a "hotspot" mutation in heptocellular carcinomas occurring in populations exposed to aflatoxin and with high prevalence of hepatitis B virus carriers (2, 3, 9, 10, 16, 24). We evaluated in this paper whether this "hotspot" mutation could be detected in cell-free DNA circulating in plasma of patients with hepatocellular carcinoma and cirrhosis in Qidong, China, and tried to illustrate the significance of the detection of this molecular biomarker. METHODS: We collected blood samples from 25 hepatocellular carcinoma patients, 20 cirrhotic patients and 30 healthy controls in Qidong area. DNA was extracted and purified from 200 μl of plasma from each sample. The 249~(Ser) p53 mutation was detected by restriction digestion analysis and direct sequencing of exon-7 PCR products. RESULTS: We found in exon 7 of p53 gene G → T transversion at the third base of codon 249 resulting 249~(Arg)→249~(Ser) mutation in 10/25 (40 %) hepatocellular carcinoma cases, 4/20 (20 %) cirrhotics, and 2/30 (7 %) healthy controls. The adjusted odds ratio for having the mutation was 22.1 (95 % CI, 3.2～91.7) for HCC cases compared to controls. CONCLUSION: These data show that the 249~(Ser) p53 mutation in plasma is strongly associated with hepatocellular carcinoma in Qidong patients. We found this mutation was also detected, although it was at a much lower frequency, in plasma DNA of Qidong cirrhotics and healthy controls; We consider that these findings, together with the usual method of HCC diagnosis, will give more information in early diagnosis of HCC, and 249~(Ser) p53 mutation should be developed to a new early diagnostic marker for HCC.
机译：目的：启东地区肝细胞癌（HCC）的特征之一是选择性突变导致p53基因第249位密码子发生丝氨酸取代（1，20），并且已被鉴定为肝细胞“热点”突变发生在暴露于黄曲霉毒素且乙型肝炎病毒携带者患病率较高的人群中的癌症（2、3、9、10、16、24）。我们在本文中评估了是否可以在中国启东的肝细胞癌和肝硬化患者血浆中循环的无细胞DNA中检测到“热点”突变，并试图说明检测这种分子生物标记物的意义。方法：我们从启东地区收集了25例肝细胞癌患者，20例肝硬化患者和30例健康对照者的血液样本。从每个样品的200μl血浆中提取并纯化DNA。通过限制性消化分析和外显子7 PCR产物的直接测序检测到249〜（Ser）p53突变。结果：在10/25（40％）肝细胞癌病例中，p53基因G的外显子7→T转换在249位密码子的第三个碱基处导致249〜（Arg）→249〜（Ser）突变，其中4/20（ 20％的肝硬化患者和2/30（7％）的健康对照者。与对照组相比，HCC患者发生突变的调整后优势比为22.1（95％CI，3.2〜91.7）。结论：这些数据表明，血浆中249〜（Ser）p53突变与启东患者的肝细胞癌密切相关。我们发现在启东肝硬化患者和健康对照者的血浆DNA中也检测到了这种突变，尽管其频率要低得多。我们认为，这些发现以及常规的HCC诊断方法将为HCC的早期诊断提供更多信息，因此249〜（Ser）p53突变应被开发为HCC的新的早期诊断标记。

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