Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis
Intratumoural cytogenetic heterogeneity of sporadic colorectal carcinomas suggests several pathways to liver metastasis
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DOI：
10.1002/path.2712
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发表时间：
2010-07-01
影响因子：
7.3
通讯作者：
Munoz-Bellvis, Luis
中科院分区：
文献类型：
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作者：
Maria Sayagues, Jose;del Mar Abad, Maria;Munoz-Bellvis, Luis
关于结直肠癌的染色体异常已经了解了很多，但是原发性和转移性肿瘤样本中存在的肿瘤克隆之间的细胞遗传学关系仍然不清楚。我们使用间期荧光原位杂交技术分析了48例肿瘤中47个染色体区域的异常频率，其中包括24例原发性结直肠癌和24例配对肝转移瘤。所有肿瘤均表现出复杂的核型，在原发肿瘤及其配对转移瘤中有7个或更多不同染色体/染色体区域的数量/结构异常。8号染色体是最常见的改变（22/24原发肿瘤），一致显示del（8p22）和/或8q24扩增，其次是整个7号染色体（21/24原发肿瘤）和染色体17p和20q（20/24原发肿瘤）异常。多染色体探针同时染色发现23/24例（46/48例）存在两个或两个以上的肿瘤细胞克隆。有趣的是，肝转移通常含有与原发肿瘤相似的肿瘤细胞克隆，这表明特异性肿瘤克隆缺乏选择性选择。尽管如此，在23/24例转移性肿瘤中检测到额外的染色体异常，这些异常优先由del（17p13）和11q13和20q13的获得/扩增组成；此外，与原发肿瘤相比，转移瘤显示1p、7q、8q、13q和18q染色体异常数量增加，以及涉及6、10q23、14q32、15q22和19q13染色体的新染色体异常数量。由于整个7号染色体的数值异常以及8号染色体特定区域(如del（8p22）和/或8q24的增益/扩增在伴有转移的原发性结直肠癌肿瘤中出现的频率很高，因此建议在诊断时对其进行评估，对于识别具有较高肝转移风险的结直肠癌患者具有重要的临床应用价值。版权所有(C) 2010英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Much has been learned about the chromosomal abnormalities of colorectal carcinomas but the cytogenetic relationship between the neoplastic clones present in primary versus metastatic tumour samples remains unclear. We analyse the frequency of abnormalities for 47 chromosome regions using the interphase fluorescence in situ hybridization technique in a group of 48 tumours, including 24 primary colorectal tumours and 24 paired liver metastases. All tumours showed complex karyotypes with numerical/structural abnormalities for seven or more different chromosomes/chromosome regions both in the primary tumours and in their paired metastases. Chromosome 8 was the most frequently altered (22/24 primary tumours), consistently showing del(8p22) and/or gains/amplification of 8q24, followed by abnormalities of the entire chromosome 7 (21/24 primary tumours) and of chromosomes 17p and 20q (20/24 primary tumours). Simultaneous staining for multiple chromosome probes revealed the presence of two or more tumour cell clones in 23/24 cases (46/48 tumour samples). Interestingly, the liver metastases typically contained tumour cell clones similar to those found in the primary tumours, suggesting the absence of selective selection of specific tumour clones. Despite this, additional chromosomal abnormalities were detected in 23/24 metastatic tumours, which preferentially consisted of del(17p13) and gains/amplification of 11q13 and 20q13; moreover, compared to primary tumours, metastases showed an increased number of abnormalities of chromosomes 1p, 7q, 8q, 13q, and 18q, and new chromosomal abnormalities involving chromosomes 6, 10q23, 14q32, 15q22, and 19q13. Owing to the high frequency of numerical abnormalities of the entire chromosome 7 and loss and/or gain/amplification of specific regions of chromosome 8, eg del(8p22) and/or gains/amplification of 8q24 in primary colorectal tumours with associated metastases, it is suggested that their assessment at diagnosis could be of great clinical utility for the identification of colorectal cancer patients at higher risk of developing liver metastases. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.