LOSS OF HETEROZYGOSITY SUGGESTS TUMOR SUPPRESSOR GENE RESPONSIBLE FOR PRIMARY HEPATOCELLULAR-CARCINOMA
LOSS OF HETEROZYGOSITY SUGGESTS TUMOR SUPPRESSOR GENE RESPONSIBLE FOR PRIMARY HEPATOCELLULAR-CARCINOMA
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DOI：
10.1073/pnas.86.22.8852
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发表时间：
1989-11-01
影响因子：
11.1
通讯作者：
GOVINDARAJAH, S
中科院分区：
文献类型：
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作者：
BUETOW, KH;MURRAY, JC;GOVINDARAJAH, S
原发性肝细胞癌（PHC），流行病学上与慢性B肝炎病毒（HBV）感染有关，历史上被认为是由癌基因的激活或引入引起的。然而，来自人PHC的转化序列尚未被可重复地分离。在本文中，有证据表明，PHC可能会导致相反的抗癌基因的丢失。7 12人原发性肝肿瘤的限制性片段长度多态性（RFLP）的面板测试证明4号染色体上的标志物的组成杂合性丢失。对肿瘤和非肿瘤肝组织进行11个4号染色体RFLPs分型。此外，测试了其他9条染色体（1、2、6、7、9、11、13、14和17）上的至少一个RFLP的等位基因丢失。在9例染色体4q标记组成性杂合的肿瘤中，7例显示肿瘤组织中的等位基因丢失。七个样品中的六个对于4p和4q标记都是联合信息的。6个中的5个仅表现出4q RFLP的丢失。在一个个体中，其中两个样本取自同一肿瘤内的远处位置，两个样本均显示相同等位基因的丢失。在提供等位基因丢失信息的其他染色体中，一个肿瘤在13 q上显示出变化。没有观察到其他变化，位于其他八条染色体上的RFLP测试。这些结果表明，抑癌基因可能位于4q，并提出了HPC和其他癌症的血清流行病学相关的病毒感染的机制。由慢性HBV感染或其他环境因素引起的肝癌可能通过导致位于4号染色体上的肿瘤抑制基因座（抑癌基因）丢失的遗传事件联系起来。
Primary hepatocellular carcinoma (PHC), epidemiologically associated with chronic hepatitis B virus (HBV) infection, has historically been felt to be caused by the activation or introduction of an oncogene. However, transforming sequences from human PHC have not been reproducibly isolated. In this paper, evidence is presented that suggests PHC may result instead from the loss of an anti-oncogene. Seven of 12 human primary liver tumors tested against a panel of restriction fragment length polymorphisms ( RFLPs) demonstrated loss of constitutional heterozygosity for markers on chromosome 4. Tumor and nontumor liver tissue were typed for 11 chromosome 4 RFLPs. In addition, at least one RFLP on nine other chromosomes (1, 2, 6, 7, 9, 11, 13, 14, and 17) was tested for allelic loss. Seven of nine tumors constitutionally heterozygous for chromosome 4q markers showed allele loss in tumor tissue. Six of the seven samples were jointly informative for both 4p and 4q markers. Five of the six demonstrated loss for only 4q RFLPs. In one individual, in which two samples were taken from distant locations within the same tumor, both samples showed loss of the same alleles. Among the other chromosomes informative for allele loss, one tumor showed changes on 13q. No other changes were observed in RFLPs located on the eight other chromosomes tested. These results indicate that an anti-oncogene may be located on 4q and suggest a mechanism for HPC and other cancers seroepidemiologically related to virus infection. Liver cancer caused by chronic HBV infection or other environmental agents may be linked through genetic events responsible for the loss of a tumor suppressor locus (anti-oncogene) located on chromosome 4.