Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization
Assessment of differentiation and progression of hepatic tumors using array-based comparative genomic hybridization
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DOI：
10.1016/j.cgh.2006.07.010
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发表时间：
2006-10-01
影响因子：
12.6
通讯作者：
Wilkens, Ludwig
中科院分区：
文献类型：
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作者：
Steinemann, Doris;Skawran, Britta;Wilkens, Ludwig
背景与目的：为了进一步了解导致肝细胞腺瘤（HCA）和肝细胞癌（HCC）去分化的分子机制，我们对24例HCC和10例HCA进行了高分辨率阵列比较基因组杂交（array-CGH）。方法：采用含有6251个细菌人工染色体/质粒人工染色体克隆的DNA芯片。他们允许全基因组分辨率为1mb，对于人类肿瘤中经常涉及的染色体区域以及包含已知肿瘤抑制基因和致癌基因的区域，分辨率甚至更高，可达100kb。结果：在所有病例中，通过基于阵列的比较基因组杂交发现基因组尺度上拷贝数的变化。在HCC中，染色体1q区增加（91.6%）、8q区增加（58.3%）、8p区减少（54%）最为常见。层次聚类分析将所有HCA从HCC中分离出来。然而，在2例已知糖原病史的I型和肝腺瘤病腺瘤中也发现了1q的增加。临界获得的区域被缩小到波段1q22-23。虽然腺瘤和高分化癌的平均染色体畸变数无显著差异（2.7 vs 4.6），但随着HCC去分化，染色体畸变数显著增加（HCC- g2为14.1，HCC- g2 /3为16.3,P < 0.02）。HCC的去分化也与4q和13q的损失密切相关（P分别< 0.001和< 0.005）。结论：HCC去分化过程中染色体不稳定性的增加导致染色体结构畸变的积累和特定染色体区域的损失和获得。
Background & Alms: To gain more information about the molecular mechanisms leading to dedifferentiation of hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC), high-resolution array-based comparative genomic hybridization (array-CGH) was performed on 24 cases of HCC and 10 cases of HCA. Methods: DNA chips containing 6251 individual bacterial artificial chromosome/plasmid artificial chromosome clones were used. They allowed for a genome-wide resolution of 1 Mb and an even higher resolution of up to 100 kb for chromosome regions recurrently involved in human tumors and for regions containing known tumor-suppressor genes and oncogenes. Results: Copy number changes on the genomic scale were found by array-based comparative genomic hybridization in all cases. In HCC, gains of chromosomal regions 1q (91.6%), and 8q (58.3%), and losses of 8p (54%) were found most frequently. Hierarchic cluster analysis branched all HCA from HCC. However, in 2 adenomas with a known history of glycogenosis type I and adenomatosis hepatis gains of 1q were found, too. The critically gained region was narrowed down to bands 1q22-23. Although no significant differences in the mean number of chromosomal aberrations were seen between adenomas and well-differentiated carcinomas (2.7 vs 4.6), a significant increase accompanied the dedifferentiation of HCC (14.1 in HCC-G2 and 16.3 in HCC-G2/3; P < .02). Dedifferentiation of HCC also was correlated closely to losses of 4q and 13q (P < .001 and < .005, respectively). Conclusions: The increased chromosomal instability during dedifferentiation of HCC leads to an accumulation of structural chromosomal aberrations and losses and gains of defined chromosome regions.