Chromosomal imbalances of primary and metastatic lung adenocarcinomas
Chromosomal imbalances of primary and metastatic lung adenocarcinomas
复制标题
DOI：
10.1002/path.1009
复制
发表时间：
2002-01-01
影响因子：
7.3
通讯作者：
Petersen, I
中科院分区：
文献类型：
--
作者：
Goeze, A;Schlüns, K;Petersen, I
应用比较基因组杂交技术(CGH)对60例83例肺腺癌患者进行了染色体异常筛查。最常见的改变是染色体1q上的DNA过度表达，73%的原发肿瘤以1q22-q23为高峰，其次是8q和20q上的DNA过度表达，3p、4q、6q、9p、9q和13q上的DNA缺失至少占60%。转移性和非转移性肿瘤的差异直方图的产生和23例原发肿瘤和相应转移瘤配对样本的逐例直方图的比较表明，染色体3p12-p14、3p22-p24、4p13-15.1、4q21-qTER、6q21-qTER、8p、10q、14q21、17p12-p13、20p12和21q的缺失和1q21-q25、7q11.2、9q34、11q12-q13、14q11-q13和17q25上的过度表达与转移表型有关。相反，19号染色体的缺失和3p、4q、5p和6q的增加优先发现在非转移性肿瘤中。对配对样本的分析显示出相当大的染色体不稳定性，但在每个病例中都表明了克隆关系。原发肿瘤经常表现出额外的缺失，这表明功能突变的丧失在肿瘤扩散的初始阶段是关键的，而转移瘤优先获得DNA获得，可能调节转移表型。这项研究的主要数据(比率分布、临床病理参数、直方图)也可在http://amba.charite.de/cgh.上获得版权所有(C)2001 John Wiley Sons，Ltd.
Comparative genomic hybridization (CGH) was used to screen 83 lung adenocarcinomas of 60 patients for chromosomal imbalances. The most common alteration was DNA overrepresentation on chromosome 1q, with a peak incidence at 1q22-q23 in 73% of the primary tumours, followed by DNA overrepresentation on chromosomes 8q and 20q, and deletions on chromosomes 3p, 4q, 6q, 9p, 9q, and 13q, in at least 60%. The generation of a difference histogram of metastasizing versus non-metastasizing tumours and a case-by-case histogram for the comparison of 23 paired samples of primary tumours and corresponding metastases suggested that deletions on chromosomes 3p12-p14, 3p22-p24, 4p13-15.1, 4q21-qter, 6q21-qter, 8p, 10q, 14q21, 17p12-p13, 20p12, and 21q, and overrepresentations on chromosomes 1q21-q25, 7q11.2, 9q34, 11q12-q13, 14q11-q13, and 17q25 are associated with the metastatic phenotype. In contrast, losses on chromosome 19 and gains on 3p, 4q, 5p, and 6q were preferentially found in non-metastasizng tumours. The analysis of the paired samples revealed considerable chromosomal instability, but indicated a clonal relationship in each case. The primary tumours often showed additional deletions, suggesting that loss of function mutations are critical in the initial phase of tumour dissemination, whereas the metastases preferentially acquired DNA gains, probably modulating the metastatic phenotype. The primary data from this study (ratio profiles, clinicopathological parameters, histograms) are also available at http://amba.charite.de/cgh. Copyright (C) 2001 John Wiley Sons, Ltd.