Lambros Maryou B K, Fiegler Heike, Jones Angela, Gorman Patricia, Roylance Rebecca R, Carter Nigel P, Tomlinson Ian P M
Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK.
J Pathol. 2005 Jan;205(1):29-40. doi: 10.1002/path.1681.
In this study, 23 ovarian cancer cell lines were screened using array-comparative genomic hybridization (aCGH) based on large-insert clones at about 1 Mb density from throughout the genome. The most frequent recurrent changes at the level of the chromosome arm were loss of chromosome 4 or 4q, loss of 18q and gain of 20 or 20q; other recurrent changes included losses of 6q, 8p, 9p, 11p, 15q, 16q, 17p, and 22q, and gain of 7q. Losses of 4q and 18q occurred together more often than expected. Evidence was found for two types of ovarian cancer, one typically near-triploid and characterized by a generally higher frequency of chromosomal changes (especially losses of 4p, 4q, 13q, 15q, 16p, 16q, 18p and 18q), and the other typically near-diploid/tetraploid and with fewer changes overall, but with relatively high frequencies of 9p loss, 9q gain, and 20p gain. Multiple novel changes (amplifications, homozygous deletions, discrete regions of gain or loss, small overlapping regions of change and frequently changed clones) were also detected, each of which might indicate the locations of oncogenes or tumour suppressor loci. For example, at least two regions of amplification on chromosome 11q13, one including cyclin D1 and the other the candidate oncogene PAK1, were found. Amplification on 11q22 near the progesterone receptor gene and a cluster of matrix metalloproteinase loci was also detected. Other potential oncogenes, which mapped to regions found by this study, included cyclin E and PIK3C2G. Candidate tumour suppressor genes in regions of loss included CDKN2C, SMAD4-interacting protein and RASSF2.
在本研究中,使用基于全基因组约1 Mb密度的大插入片段克隆的阵列比较基因组杂交(aCGH)技术,对23个卵巢癌细胞系进行了筛选。染色体臂水平上最常见的反复发生的变化是4号或4q染色体缺失、18q染色体缺失以及20号或20q染色体增加;其他反复发生的变化包括6q、8p、9p、11p、15q、16q、17p和22q染色体缺失以及7q染色体增加。4q和18q染色体缺失同时出现的频率高于预期。发现了两种类型的卵巢癌,一种通常接近三倍体,其特征是染色体变化频率普遍较高(特别是4p、4q、13q、15q、16p、16q、18p和18q染色体缺失),另一种通常接近二倍体/四倍体,总体变化较少,但9p染色体缺失、9q染色体增加和20p染色体增加的频率相对较高。还检测到多个新的变化(扩增、纯合缺失、增益或缺失的离散区域、小的重叠变化区域和频繁变化的克隆),每一个变化都可能指示癌基因或肿瘤抑制基因座的位置。例如,在11q13染色体上发现了至少两个扩增区域,一个区域包含细胞周期蛋白D1,另一个区域包含候选癌基因PAK1。在孕激素受体基因附近的11q22染色体上以及一组基质金属蛋白酶基因座处也检测到了扩增。其他映射到本研究发现区域的潜在癌基因包括细胞周期蛋白E和PIK3C2G。缺失区域中的候选肿瘤抑制基因包括CDKN2C、SMAD4相互作用蛋白和RASSF2。