ALLELE LOSS ON CHROMOSOME-16 ASSOCIATED WITH PROGRESSION OF HUMAN HEPATOCELLULAR-CARCINOMA
ALLELE LOSS ON CHROMOSOME-16 ASSOCIATED WITH PROGRESSION OF HUMAN HEPATOCELLULAR-CARCINOMA
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DOI：
10.1073/pnas.87.17.6791
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
HIROHASHI, S
中科院分区：
文献类型：
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作者：
TSUDA, H;ZHANG, WD;HIROHASHI, S
16号染色体杂合性缺失是人类肝细胞癌常见的基因改变。为了阐明16号染色体等位基因缺失的致病意义，我们用15个16号染色体多态DNA标记对70例手术切除的肿瘤进行了限制性片段长度多态性分析。在69例信息性病例中，36例(52%)检测到16号染色体杂合性缺失，这36例肿瘤的常见等位基因缺失区域位于Hp(16q22.1)和CTRB(16q22.3-q23.2)之间。这些缺失更多发生在分化较差、体积较大和有转移的肝癌中，而在最早阶段的肝癌中没有检测到。此外，这些丢失与是否存在乙肝病毒DNA整合或丙型肝炎病毒感染无关。这些结果表明，16号染色体杂合性缺失是肝癌发生后的晚期事件，并强烈提示这一现象与肝癌进展过程中肿瘤侵袭性的增强有关。
Loss of heterozygosity on chromosome 16 is a common genetic alteration in human hepatocellular carcinoma (HCC). To clarify the pathogenetic significance of allele loss on chromosome 16, we performed restriction fragment length polymorphism analysis of 70 surgically resected tumors by using 15 polymorphic DNA markers for chromosome 16. Loss of heterozygosity on chromosome 16 was detected in 36 (52%) of 69 informative cases, and the common region of allele loss in these 36 tumors was located between the HP locus (16q22.1) and the CTRB locus (16q22.3-q23.2). These losses occurred more frequently in HCCs of poor differentiation, of larger size, and with metastasis, whereas they were not detected in HCC at the earliest stage. In addition, these losses were not associated with presence or absence of hepatitis B virus DNA integration or hepatitis C virus infection. These results show that loss of heterozygosity on chromosome 16 is a late event occurring after hepatocarcinogenesis and strongly suggest that this phenomenon is involved in enhancement of tumor aggressiveness during progression of HCC.