Germ-line mutations of the p16(INK4)(MTS1) gene occur in a subset of patients with hepatocellular carcinoma
Germ-line mutations of the p16(INK4)(MTS1) gene occur in a subset of patients with hepatocellular carcinoma
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DOI：
10.1002/hep.510250613
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发表时间：
1997-06-01
期刊：
影响因子：
13.5
通讯作者：
Shaw, P
中科院分区：
文献类型：
--
作者：
Chaubert, P;Gayer, R;Shaw, P
肝癌发生的分子机制知之甚少。我们分析了26例不同病因的肝细胞癌患者的p16（INK4）（MTS1）基因的状态，其中4例患者携带p16（INK4）（MTS1）基因的半合子种系点突变，提示存在家族性肝细胞癌，这4例患者中有2例野生型等位基因在肿瘤中丢失，其中3例携带生殖系突变的患者患有非肝硬化相关的HCC。在26例HCC中未发现p16（INK4）（MTS1）的体细胞突变。HCC中p16（INK4）（MTS1）基因最常见的体细胞改变是从头甲基化，在48%的病例中检测到。p16（INK4）（MTS1）基因等位基因丢失率低（21%）。总之，这些结果表明，p16（INK4）（MTS1）基因的改变在HCC的发生中起着重要作用。
The molecular mechanisms of hepatocarcinogenesis are poorly understood. Only very recently has there been a suggestion of familial hepatocellular carcinoma (HCC), We have analyzed the status of the p16(INK4)(MTS1) gene, a cyclin-dependent kinase inhibitor, in 26 patients with HCC of different etiologies, Four patients carried hemizygous germ-line point mutations of the p16(INK4)(MTS1) gene, suggesting the existence of familial HCC involving this gene, The wild-type allele was lost in the tumor in 2 of these 4 patients, Three of the patients carrying a germ-line mutation had non-cirrhosis-associated HCC. No somatic mutations of p16(INK4)(MTS1) were observed in the 26 cases of HCC. The most common somatic alteration of the p16(INK4)(MTS1) gene in HCC was de novo methylation, which was detected in 48% of the cases. Lour levels (21%) of p16(INK4)(MTS1) gene allele loss were observed. Altogether, these results indicate that alteration of the p16(INK4)(MTS1) gene plays an important role in the genesis of HCC.