Diep Chieu B, Parada Luis A, Teixeira Manuel R, Eknaes Mette, Nesland Jahn M, Johansson Bertil, Lothe Ragnhild A
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Genes Chromosomes Cancer. 2003 Feb;36(2):189-97. doi: 10.1002/gcc.10162.
The majority of genetic studies of colorectal carcinogenesis have focused on changes found in primary tumors. Despite the fact that liver metastases are a leading cause of colorectal cancer deaths, the molecular genetic basis of the advanced disease stages remains poorly understood. We performed comparative genomic hybridization (CGH) on 17 liver metastases from colorectal carcinomas and compared the quantitative profile with the qualitative profile previously obtained with chromosome banding. An average of 12.6 aberrations per tumor was found by CGH. Chromosome 18 and chromosome arms 4q, 8p, and 17p were most frequently lost, whereas chromosomes 7 and 20 and chromosome arms 6p, 8q, and 13q were most frequently gained. We compared the chromosome banding and CGH data after converting the karyotypes into net copy number gains and losses. Ten tumors showed agreement between the findings of the two techniques, whereas five tumors did not (in two cases, no mitotic cells were obtained for banding analysis). All five discordant cases had a "simple" abnormal or normal karyotype, but revealed multiple changes by CGH. A likely explanation for this discrepancy is that in vitro growth before G-banding selected against the cancer cells. Interestingly, by comparing the CGH profiles of the "complex" vs. the "simple"/normal karyotype groups, deletion of 8p and gain of 16q were seen more frequently in the former group. The liver metastases had the same aberrations as seen in primary colorectal carcinomas, summarized in a literature survey. However, these aberrations were seen more frequently in liver metastases, which may be attributable to increased genetic instability.
大多数关于结直肠癌发生的遗传学研究都集中在原发性肿瘤中发现的变化。尽管肝转移是结直肠癌死亡的主要原因，但晚期疾病阶段的分子遗传学基础仍知之甚少。我们对17例结直肠癌肝转移灶进行了比较基因组杂交（CGH），并将定量图谱与先前通过染色体显带获得的定性图谱进行了比较。通过CGH发现每个肿瘤平均有12.6个畸变。18号染色体以及4q、8p和17p染色体臂最常发生缺失，而7号和20号染色体以及6p、8q和13q染色体臂最常发生增益。在将核型转换为净拷贝数增益和损失后，我们比较了染色体显带和CGH数据。10个肿瘤的两种技术结果一致，而5个肿瘤不一致（在2例中，未获得用于显带分析的有丝分裂细胞）。所有5例不一致的病例都有“简单”的异常或正常核型，但通过CGH显示出多个变化。这种差异的一个可能解释是，G显带之前的体外生长选择淘汰了癌细胞。有趣的是，通过比较“复杂”核型组与“简单”/正常核型组的CGH图谱，在前一组中8p缺失和16q增益更为常见。文献调查总结显示，肝转移灶具有与原发性结直肠癌相同的畸变。然而，这些畸变在肝转移灶中更常见，这可能归因于遗传不稳定性增加。
