Yeh S H, Chen P J, Chen H L, Lai M Y, Wang C C, Chen D S
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei.
Cancer Res. 1994 Aug 1;54(15):4188-92.
Cytogenetic analysis of hepatocellular carcinoma (HCC) cell lines and primary HCC tissues has demonstrated chromosome 1p to be the region most commonly affected. To refine the altered locus, genetic abnormalities of this region were surveyed systemically by microsatellite polymorphism analysis. Twelve sets of primers evenly distributed on chromosome 1p which can amplify di- or tetranucleotide repeat length polymorphism by polymerase chain reaction were selected. The results were then supplemented by the conventional restriction fragment length polymorphism study. A comparison of the allele patterns between 30 pairs of HCC and their corresponding nontumor DNAs discovered chromosome 1p aberrations in 15 of 30 tumors (50%). The abnormalities can be classified into three groups. The first aberration was typical loss of heterozygosity that was found in 9 HCCs (30%). The second aberration was a 2-3-fold increase of allelic dosage, which was detected in 6 HCCs (20%). The third aberration was the novel microsatellite polymorphism, which was detected in 3 cases (10%). These abnormalities seemed to cluster at the distal part of chromosome 1p, with a common region mapped to 1p35-36, which is also the region with frequent loss of heterozygosity in neuroblastoma and colorectal and breast cancers. Therefore, loss of putative tumor suppressor gene(s) in this locus may participate in the development of hepatocellular carcinoma and a wide range of human cancers.
对肝癌（HCC）细胞系和原发性肝癌组织进行的细胞遗传学分析表明，1号染色体短臂（1p）是最常受影响的区域。为了精确定位改变的位点，通过微卫星多态性分析对该区域的基因异常进行了系统研究。选择了12组均匀分布在1号染色体短臂上的引物，这些引物可通过聚合酶链反应扩增二核苷酸或四核苷酸重复长度多态性。然后通过传统的限制性片段长度多态性研究对结果进行补充。比较30对肝癌及其相应的非肿瘤DNA的等位基因模式，发现30个肿瘤中有15个（50%）存在1号染色体短臂畸变。这些异常可分为三组。第一种畸变是典型的杂合性缺失，在9例肝癌中发现（30%）。第二种畸变是等位基因剂量增加2至3倍，在6例肝癌中检测到（20%）。第三种畸变是新型微卫星多态性，在3例中检测到（10%）。这些异常似乎集中在1号染色体短臂的远端，共同区域定位于1p35 - 36，这也是神经母细胞瘤、结直肠癌和乳腺癌中杂合性频繁缺失的区域。因此，该位点假定的肿瘤抑制基因的缺失可能参与了肝细胞癌和多种人类癌症的发生发展。
