Knösel Thomas, Petersen Simone, Schwabe Holger, Schlüns Karsten, Stein Ulrike, Schlag Peter Michael, Dietel Manfred, Petersen Iver
Institute of Pathology, University Hospital Charité, Berlin, Germany.
Virchows Arch. 2002 Feb;440(2):187-94. doi: 10.1007/s004280100493.
Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.
采用比较基因组杂交（CGH）技术对54例晚期结肠癌（即24例原发性肿瘤和30例转移瘤）进行染色体改变筛查。运用一种敏感的统计方法来确定DNA失衡情况，并通过直方图分析改变的发生率，我们发现20q染色体的DNA过度代表是最常见的改变，存在于100%的病例中。在18q21 - 18q23（96%）、4q27 - 4q28（96%）、4p14（87%）、5q21（81%）、1p21 - 1p22（72%）、21q21（74%）、6q16（72%）、3p12（66%）、8p24 - 8p21（66%）、9p21（64%）、11q22（64%）以及14q13 - 14q21（64%）观察到高频率缺失。在7q12 - 7q11.2（75%）、16p11 - 16p12（70%）、19p13（70%）、9q34（67%）、19q13（67%）、13q34（64%）、13q13（64%）、17q21（59%）、22q11（61%）、8q24（57%）和1q21（57%）发现进一步频繁的过度代表。明显的DNA增加和减少分别定义为比率谱超过1.5和0.5值的区域，它们经常与发生率曲线的峰值共定位。使用差异直方图比较肿瘤亚组以及逐个病例的直方图分析15对配对肿瘤样本，确定上述几种改变与肿瘤进展和转移形成相关。该研究确定了其他位点，并更精确地描绘了先前已报道的那些位点。为了进行比较，我们已将主要数据（比率谱、临床病理参数、直方图）发布在交互式网站http://amba.charite.de/cgh上，在该网站可以确定各个位点的改变发生率，并可应用其他参数分析我们的CGH结果。
