Chaubert P, Gayer R, Zimmermann A, Fontolliet C, Stamm B, Bosman F, Shaw P
Institut Universitaire de Pathologie, Lausanne, Switzerland.
Hepatology. 1997 Jun;25(6):1376-81. doi: 10.1002/hep.510250613.
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 p16INK4(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 p16INK4(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 p16INK4(MTS1) were observed in the 26 cases of HCC. The most common somatic alteration of the p16INK4(MTS1) gene in HCC was de novo methylation, which was detected in 48% of the cases. Low levels (21%) of p16INK4(MTS1) gene allele loss were observed. Altogether, these results indicate that alteration of the p16INK4(MTS1) gene plays an important role in the genesis of HCC.
肝癌发生的分子机制目前仍知之甚少。直到最近才有关于家族性肝细胞癌（HCC）的报道。我们分析了26例不同病因的肝癌患者中细胞周期蛋白依赖性激酶抑制剂p16INK4（MTS1）基因的状态。4例患者携带p16INK4（MTS1）基因的半合子种系点突变，提示存在涉及该基因的家族性肝癌。这4例患者中有2例的肿瘤中野生型等位基因缺失。3例携带种系突变的患者患有非肝硬化相关性肝癌。在26例肝癌病例中未观察到p16INK4（MTS1）的体细胞突变。肝癌中p16INK4（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。观察到低水平（21%）的p16INK4（MTS1）基因等位基因缺失。总之，这些结果表明p16INK4（MTS1）基因的改变在肝癌的发生中起重要作用。
