Kishimoto Y, Shiota G, Wada K, Kitano M, Nakamoto K, Kamisaki Y, Suou T, Itoh T, Kawasaki H
Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago, Japan.
J Cancer Res Clin Oncol. 1996;122(10):585-9. doi: 10.1007/BF01221189.
Most hepatocellular carcinoma (HCC) is preceded by liver cirrhosis, but the genetic changes involved in cirrhosis are not well understood. We therefore studied loss of heterozygosity (LOH) in cirrhotic and neoplastic foci in livers of 14 patients with HCC. The samples, microdissected from paraffin-embedded tissues, were analyzed using a polymerase-chain-reaction-based assay for dinucleotide repeat polymorphisms on 8p. Of the 14 cases, 13 showed constitutional heterozygosity for the microsatellite markers. In 7 (54%) of these 13 informative cases, LOH was detected in the primary HCC and, in these 7 doubly informative (informative and LOH-positive in primary HCC) cases, LOH was found in 16 (70%) of 23 liver cirrhotic foci. The pattern of 8p allelic loss was identical in each doubly informative tumor; however, some of the liver cirrhotic foci harbored an 8p loss identical to that seen in the primary HCC, some harbored a different 8p loss, and some did not harbor any 8p loss. The remaining 6 cases without LOH on 8p in HCC showed no 8p loss in any cirrhotic foci. Presumably HCC could develop from cirrhotic cells harboring 8p loss.
大多数肝细胞癌（HCC）之前都有肝硬化，但肝硬化所涉及的基因变化尚不清楚。因此，我们研究了14例HCC患者肝脏中肝硬化灶和肿瘤灶的杂合性缺失（LOH）情况。从石蜡包埋组织中显微切割得到的样本，使用基于聚合酶链反应的检测方法分析8p上的二核苷酸重复多态性。14例病例中，13例显示微卫星标记的构成性杂合性。在这13例信息丰富的病例中，7例（54%）在原发性HCC中检测到LOH，在这7例双重信息丰富（信息丰富且原发性HCC中LOH阳性）的病例中，23个肝硬化灶中有16个（70%）发现有LOH。每个双重信息丰富的肿瘤中8p等位基因缺失模式相同；然而，一些肝硬化灶的8p缺失与原发性HCC中所见相同，一些有不同的8p缺失，还有一些没有8p缺失。其余6例HCC中8p无LOH的病例，在任何肝硬化灶中均未显示8p缺失。推测HCC可能由具有8p缺失的肝硬化细胞发展而来。
