Yeh S H, Chen P J, Lai M Y, Chen D S
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
Gastroenterology. 1996 Jan;110(1):184-92. doi: 10.1053/gast.1996.v110.pm8536855.
BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q. To better define the commonly affected region for further positional cloning of the putative tumor-suppressor genes contained in these two chromosome arms, microsatellite polymorphism analysis was conducted to analyze extensively the allelic loss on both chromosome loci.
DNA from 42 pairs of large hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12 sets of microsatellite polymorphic markers.
The frequency of allelic loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An even higher frequency (77%) was found on chromosome 4q with the common region mapped to 4q12-23. The allelic loss of chromosome 4q was significantly associated with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with those of normal level (91% vs. 30%; Fisher's Exact Test, two-tailed P = 1.12 x 10(-4)).
The results form the basis for further positional cloning of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression in hepatocellular carcinoma.
在人类肝细胞癌中，限制性片段长度多态性分析显示4号和16号染色体上频繁出现等位基因缺失。为了更好地确定这两条染色体臂中所含假定肿瘤抑制基因的常见受累区域，以便进一步进行定位克隆，我们进行了微卫星多态性分析，广泛分析这两个染色体位点上的等位基因缺失情况。
制备了42对大肝细胞癌（>5 cm）及相应的非肿瘤性肝组织的DNA。通过13组或12组微卫星多态性标记物研究4号和16号染色体上的等位基因缺失情况。
16号染色体上等位基因缺失的频率为70%，常见区域定位于16q22 - 23。4号染色体上发现了更高的频率（77%）且常见区域定位于4q12 - 23。4号染色体的等位基因缺失与血清甲胎蛋白升高的肝细胞癌显著相关，但与甲胎蛋白水平正常的肝细胞癌无关（91%对30%；Fisher精确检验，双侧P = 1.12×10⁻⁴）。
这些结果为进一步定位克隆4号和16号染色体上的假定肿瘤抑制基因奠定了基础。此外，4号染色体上的基因可能为肝细胞癌中甲胎蛋白表达的机制提供线索。
