Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors.
Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors.
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发表时间：
1995-05
期刊：
影响因子：
8
通讯作者：
A. T. D. Souza;G. R. Hankins;M. Washington;R. Fine;T. Orton;R. Jirtle
中科院分区：
文献类型：
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作者：
A. T. D. Souza;G. R. Hankins;M. Washington;R. Fine;T. Orton;R. Jirtle
甘露糖6-磷酸/胰岛素样生长因子II受体（M6P/IGFIIr）是激活转化生长因子β所必需的，之前我们发现其在大鼠和人肝细胞癌（hcc）中的表达显著降低。因此，我们假设M6P/IGFIIr基因的缺失可能在机制上参与了肝癌发生。利用聚合酶链反应，我们利用M6P/IGFIIr基因3'非翻译区的两个多态性来筛选非肝硬化肝炎病毒阴性肝细胞肿瘤患者的LOH。36例患者中有22例（61%）为信息型（杂合型），14/22（64%）肝肿瘤存在LOH；11/16（69%）为癌，1/3（33%）为纤维板层瘤，2/3（67%）为腺瘤。这是人类肝细胞肿瘤中M6P/IGFIIr位点的LOH的首次报道，腺瘤中LOH的存在表明等位基因丢失可能是hcc病因学的早期事件。这些结果支持了M6P/IGFIIr基因可能在肝脏中作为肿瘤抑制基因起作用的假设。
The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIr) is required for the activation of transforming growth factor beta, and previously we have found its expression to be significantly reduced in both rat and human hepatocellular carcinomas (HCCs). Therefore, we have postulated that loss of the M6P/IGFIIr gene may be mechanistically involved in liver carcinogenesis. Using the polymerase chain reaction, we utilized two polymorphisms in the 3' untranslated region of the M6P/IGFIIr gene to screen non-cirrhotic, hepatitis virus negative patients with hepatocellular tumors for LOH. Twenty-two of 36 (61%) patients were informative (heterozygous), and 14/22 (64%) liver tumors had LOH; 11/16 (69%) carcinomas, 1/3 (33%) fibrolamellar tumors and 2/3 (67%) adenomas. This is the first report of LOH at the M6P/IGFIIr locus in human hepatocellular tumors, and the presence of LOH in adenomas suggests that allelic loss may be an early event in the etiology of HCCs. These results support the hypothesis that the M6P/IGFIIr gene may function as a tumor suppressor gene in the liver.