A copy number gain of the 6p arm is linked with advanced hepatocellular carcinoma: an array-based comparative genomic hybridization study

A copy number gain of the 6p arm is linked with advanced hepatocellular carcinoma: an array-based comparative genomic hybridization study
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DOI:
10.1002/path.2491
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发表时间:
2009-04-01
影响因子:
7.3
通讯作者:
Sasaki, Kohsuke
Sasaki, Kohsuke
中科院分区:
医学1区
文献类型:
--
作者:
Chochi, Yasuyo;Kawauchi, Shigeto;Sasaki, Kohsuke

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随着癌症的发展,基因组畸变在癌细胞中逐步积累。然而,是否存在与肿瘤进展相关的基因组变化仍不清楚。本研究的目的是阐明基因组改变与肝细胞癌(HCC)临床分期之间的关系。采用1440个BAC克隆DNA芯片标记的阵列CGH技术,对42例手术切除的hcc进行DNA拷贝数畸变检测。染色体1q、8q和Xq区域拷贝数频繁增加。特别是,在超过65%的肿瘤中检测到Iq42.12、Iq43和8q24.3的增加。在染色体1p, 4q, 6q, 8p和17p区域检测到频繁的拷贝数丢失。在超过55%的hcc中检测到8p21和17p13的缺失。然而,6p和8q24.12克隆的DNA拷贝数增加在III/IV期肿瘤中比在I/II期肿瘤中更常见(p < 0.001)。特别是,整个6p的增加实际上仅限于晚期hcc。整个6p的增加被认为是hcc晚期的基因组标记。因此,这些观察结果支持HCC基因组分期的概念。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
In accordance with cancer progression, genomic aberrations accumulate in cancer cells in a stepwise fashion. However, whether there are genomic changes linked with tumour progression remains unclarified. The purpose of this study is to elucidate the relationship between genomic alterations and clinical stages in hepatocellular carcinoma (HCC). A technology of array-based CGH using DNA chips spotted with 1440 BAC clones was applied to 42 surgically removed HCCs to examine the DNA copy number aberrations. A frequent copy number gain was detected on chromosomal regions 1q, 8q and Xq. In particular, gains of Iq42.12, Iq43 and 8q24.3 were detected in more than 65% of tumours. A frequent copy number loss was detected on chromosomal regions 1p, 4q, 6q, 8p and 17p. Losses of 8p21 and 17p13 were detected in more than 55% of HCCs. However, the DNA copy number gains of clones on 6p and 8q24.12 were more frequent in stage III/IV tumours than in stage I/II tumours (p < 0.001). In particular, the gain of the whole 6p was virtually limited to advanced-staged HCCs. The gain of the whole 6p is suggested to be a genomic marker for the late stages in HCCs. These observations therefore support the concept of genomic staging in HCC. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.