Analysis of colorectal tumor progression by microdissection and comparative genomic hybridization
Analysis of colorectal tumor progression by microdissection and comparative genomic hybridization
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DOI：
10.1002/gcc.10201
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发表时间：
2003-08-01
影响因子：
3.7
通讯作者：
Hammond, DW
中科院分区：
文献类型：
--
作者：
Alcock, HE;Stephenson, TJ;Hammond, DW
本研究旨在确定结肠直肠肿瘤从腺瘤到肝转移过程中拷贝数变化的模式。17例结直肠癌的53个显微解剖亚区被划分为6个组织病理学定义的类别之一：共存腺瘤、肌层以上肿瘤、肌层内肿瘤、肿瘤穿过肠壁至浆膜脂肪、淋巴结转移和肝转移。显微解剖的样品经微波处理步骤处理，然后用作通用PCR扩增的模板。PCR产物被荧光标记并进行比较基因组杂交。所有样本的拷贝数都发生了变化，每个染色体臂（不包括外中心短臂）都受到了影响。检测到的损失多于收益，但在每个类别中观察到的变化数量之间没有显著差异。除了在每个案例中共享的变化之外，每个单独的样本都揭示了独特的变化。最常观察到的增益是X和12q。最常见的损失是8p、16p、9p、15q、18q和10q。转移性肿瘤与12q24.1或10p13-14缺失，非转移性肿瘤与8q24.1缺失，肿瘤延伸至浆膜脂肪缺失6q24-25缺失或4q11-13缺失，肿瘤延伸至浆膜脂肪与转移性病变缺失4q32-34或22q11-12，腺瘤与15q24缺失之间存在名义上的显著关联。经过多次检测校正后，4q32-34的缺失仍然非常显著。腺瘤是唯一未显示17p损失的类别。这些数据揭示了肿瘤进展的遗传异质性，少量变化与晚期疾病相关。(C) 2003 Wiley-Liss, Inc。
This investigation aimed to identify patterns of copy number change in colorectal tumor progression from adenoma to liver metastasis. Fifty-three microdissected sub-regions from 17 cases of colorectal cancer were assigned to one of six histopathologically defined categories: coexisting adenoma, tumor above the muscularis layer, tumor within the muscularis layer, tumor extending through the bowel wall to serosal fat, lymph node metastasis, and liver metastasis. Microdissected samples were treated by a microwave processing step and then used as templates for universal PCR amplification. PCR products were fluorophore labeled and subjected to comparative genomic hybridization. Copy number changes were found in all samples, and every chromosome arm (excluding acrocentric short arms) was affected. More losses than gains were detected, but there were no significant differences between the numbers of changes seen in each category. Each individual sample revealed unique changes, additional to those shared within each case. The most frequently observed gains were of X and 12q. The most common losses were of 8p, 16p, 9p, 15q, 18q, and 10q. Nominally significant associations were observed between metastatic tumor and loss of 12q24.1 or 10p13-14, non-metastatic tumor and loss of 8q24.1, tumor extending to serosal fat and loss of 6q24-25 or gain of 4q11-13, tumor extending to serosal fat and metastatic lesions and loss of 4q32-34 or 22q11-12, and adenoma and loss of 15q24. Loss of 4q32-34 remained highly significant after correction for multiple testing. Adenoma was the only category not to show loss of 17p. These data reveal a genetically heterogeneous picture of tumor progression, with a small number of changes associated with advanced disease. (C) 2003 Wiley-Liss, Inc.