Comprehensive allelotyping of well-differentiated human hepatocellular carcinoma with semiquantitative determination of chromosomal gain or loss
Comprehensive allelotyping of well-differentiated human hepatocellular carcinoma with semiquantitative determination of chromosomal gain or loss
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DOI：
10.1002/gcc.10126
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发表时间：
2002-12-01
影响因子：
3.7
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
等位基因失衡（AI），代表某些染色体的获得或损失，已经在人类肝细胞癌（HCC）中被描述，但AI对肝癌早期发生的影响尚未完全阐明。此外，以前没有等位基因研究确定导致AI的染色体获得和丢失的差异。为了解决这些问题，我们使用400个微卫星标记对18个分化良好的hcc进行了全面的等位型分析，并对染色体的增加或减少进行了半定量评估。为了有效检测等位基因增益，将等位基因失衡指数的截止值设为0.70。每个显示不平衡的等位基因进行多重PCR，使用保留的等位基因作为内部控制，以确定不平衡是染色体获得还是丢失的结果。在1q （DIS196-DIS2785, 56%）、5q （D5S647-D5S2027, 44%）、6p （6pter-D6S309, 33%）、7 （7pter-D7S657, 22%）和8q （D8S514-qter, 44%）染色体增加的频率较高，而在Ip （ipter - d1234, 22%）、8p （8pter-D8S549, 44%）和17p （17pter-D17S921, 28%）染色体丢失的频率较高。总体染色体畸变程度与最大肿瘤直径（P = 0.002）和乙型肝炎表面抗原的存在（P = 0.03）密切相关。即使在具有最小程度异常染色体的hcc中，I p和8p染色体的复发性丢失和1q和8q染色体的增加也表明这些改变在肝癌发生的早期阶段是至关重要的。另一方面，13q和16q的缺失并不常见，只在最异常的情况下才会出现，这表明这些是晚期事件。(C) 2002 Wiley-Liss, Inc。
Allelic imbalance (AI), which represents certain chromosomal gains or losses, has been described in human hepatocellular carcinoma (HCC), but the impact of AI on the early stage of hepatocarcinogenesis has not been fully clarified. Moreover, no previous allelotype studies have identified the difference in chromosomal gain and loss that results in AI. To resolve these problems, we examined 18 well-differentiated HCCs with comprehensive allelotyping by using 400 microsatellite markers with semiquantitative assessment of chromosomal gain or loss. To detect allelic gain effectively, the cutoff value of the allelic imbalance index was set at 0.70. Each allele showing imbalance was subjected to multiplex PCR with use of a retained allele as an internal control to determine whether the imbalance was the result of chromosomal gain or loss. High frequencies of chromosomal gains were detected at 1q (DIS196-DIS2785, 56%), 5q (D5S647-D5S2027, 44%), 6p (6pter-D6S309, 33%), 7 (7pter-D7S657, 22%), and 8q (D8S514-qter, 44%), whereas chromosomal losses were frequently observed at Ip (Ipter-D1S234, 22%), 8p (8pter-D8S549, 44%), and 17p (17pter-D17S921, 28%). The extent of overall chromosomal aberration was closely related to the maximum tumor diameter (P = 0.002) and the presence of hepatitis B surface antigen (P = 0.03). Recurrent chromosomal losses at I p and 8p and gains at 1q and 8q, even in HCCs with a minimal extent of aberrant chromosomes, indicate that these alterations were critical in the early stage of hepatocarcinogenesis. On the other hand, deletions of 13q and 16q were infrequent and were seen only in the most aberrant cases, which suggested that these were late events. (C) 2002 Wiley-Liss, Inc.