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目的:通过对肝细胞癌(HCC)和肝内胆管癌(ICC)之间抑癌基因(tumor suppressor gene,TSG)和微卫星(mi—crosatellite,MS)变异谱特点进行对比分析,了解这两种肝脏最常见恶性肿瘤在基因发生路径上的差异。方法:采用微组织切割法,从石蜡包埋的组织切片中提取基因组DNA进行直接测序,对33例信息性(杂合性)HCC和22例ICC进行了6种TSG杂合性缺失(loss of heterozygosity,LOH)的检测,并对其中10例HCC和全部22例ICC做7个MS的LOH分析。结果:6种TSG的变异情况在HCC依次为:p53(4/5,80.0％)、OGG1(2/4,50.0％)、APC(5/12,41.7％)、RB1(1/5,20.0％)、DCC(0/4,0％)、MCC(0/3,0％);在ICC为:APC(11/16,68.8％)、DCC(6/13,46.2％)、OGG1(5/12,41.7％)、p53(6/16,37.5％)、RB1(2/9,22.2％)、MCC(1/7,14.3％)。HCC和ICC中7个MS的LOH发生率分别为30.0％(3/10)和59.1％(13/22)。7个MS在HCC中仅有2个发生LOH,而在ICC中则全部出现LOH,其中与p16/MTS-1和MXI-1基因连锁的4个MS仅在ICC中出现LOH。结论:HCC和ICC之间TSG和MS存在着明显不同的LOH谱,推测两者在发生过程中可能沿循各自不同的分子路径。对LOH基因谱成员的分析,有助于进一步认识HCC和ICC发生的分子机制。
OBJECTIVE: To compare and analyze the characteristics of the variation of tumor suppressor gene (TSG) and microsatellite (MS) between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) The most common malignant tumor of the liver in genetically-engineered pathways. METHODS: Genomic DNA was extracted from paraffin-embedded tissue sections by direct sequencing using a tissue-based microdissection method. Six types of TSG loss of heterozygosity (heterozygous) HCC and 22 ICC were performed heterozygosity, LOH). LOH analysis of 7 MSs was performed on 10 HCCs and all 22 ICCs. Results: The variation of six kinds of TSG in HCC were as follows: p53 (4 / 5,80.0%), OGG1 (2/4, 50.0%), APC (5 / 12,41.7%), RB1 DCC (0/13, 46.2%), DCG (0/4, 0%) and MCC (0/3, 0% / 12, 41.7%), p53 (6/16, 37.5%), RB1 (2/9, 22.2%), MCC (1/7, 14.3%). The incidence of LOH in 7 MSCs in HCC and ICC was 30.0% (3/10) and 59.1% (13/22), respectively. Only seven out of seven MSHs developed LOH in HCC, while all of them showed LOH in ICC. Four MSs linked to p16 / MTS-1 and MXI-1 genes only showed LOH in ICC. CONCLUSIONS: There are obviously different LOH spectra between TSCC and MS in HCC and ICC, suggesting that they may follow different molecular pathways in the pathogenesis. The analysis of LOH gene members helps to further understand the molecular mechanism of HCC and ICC.