Genotype stability and clonal evolution of hepatocellular carcinoma assessed by autopsy-based genome-wide microsatellite analysis
Genotype stability and clonal evolution of hepatocellular carcinoma assessed by autopsy-based genome-wide microsatellite analysis
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DOI：
10.1016/j.cancergencyto.2005.02.011
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发表时间：
2005-09-01
影响因子：
--
通讯作者：
Nakao, K
中科院分区：
文献类型：
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作者：
Nishimura, T;Nishida, N;Nakao, K
染色体不稳定性是包括肝细胞癌（HCC）细胞在内的癌细胞的基本特征，这一点已被广泛接受。为了准确描述肝癌细胞克隆性演变的特征，我们研究了肝癌尸检病例中各种转移灶的染色体改变。来自主肿瘤的组织，由2个肉眼可见的不同部分组成。应用微卫星综合分析技术分析肝内转移、门静脉癌栓、网膜淋巴结转移、肺转移和非肿瘤性肝组织的微卫星分布。显示主要肿瘤不平衡的等位基因进一步进行比较双重PCR。使用保留的等位基因作为内部对照，以确定不平衡是否是染色体获得或丢失的结果。一个惊人的发现是，在主肿瘤和转移性病变中检测到的等位基因失衡几乎相同，显示为-1p，+1 q，-4q。-7、-8p、+8q、+9q、+10、-13q、-17p、+19p、-19q和- X。在主肿瘤和门静脉血栓的一部分中检测到+2 q和-16 q的额外改变。总之，在转移性进展过程中，HCC细胞的克隆性演变似乎很少见，而许多复发性染色体畸变可能在临床表现之前就已积累。(c)2005年爱思唯尔公司All rights reserved.
It is widely accepted that chromosomal instability is an essential feature of cancer cells including hepatocellular carcinoma (HCC) cells. For an accurate characterization of clonal evolution of HCC cells, we studied chromosomal alterations in various metastatic lesions in an autopsy case of HCC. Tissues from the main tumor, which consisted of 2 macroscopically distinct portions. and from intrahepatic metastasis, portal vein thrombus, epiploic lymph node metastasis, and Pulmonary metastasis as well as from the non-tumorous liver were analyzed with comprehensive microsatellite analysis. Alleles showing imbalance of the main tumor were further subjected to comparative duplex PCR. with use of a retained allele as an internal control, to determine whether the imbalance was the result of chromosomal gain or loss. A striking finding was that allelic imbalances detected in the main tumor and metastatic lesions were almost identical, showing -1p, + 1q, -4q. -7, -8p, + 8q, + 9q, + 10, - 13q, - 17p, + 19p, - 19q, and - X. Additional alterations of + 2q and - 16q were detected in one portion of the main tumor and the portal vein thrombus. In conclusion, clonal evolution of the HCC cells during metastatic progression seems rare, in contrast to many recurrent chromosomal aberrations that may have accumulated before the clinical manifestation. (c) 2005 Elsevier Inc. All rights reserved.