Molecular inversion probe analysis of gene copy alterations reveals distinct categories of colorectal carcinoma
Molecular inversion probe analysis of gene copy alterations reveals distinct categories of colorectal carcinoma
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DOI：
10.1158/0008-5472.can-06-0595
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发表时间：
2006-08-15
期刊：
影响因子：
11.2
通讯作者：
Davis, Ronald W.
中科院分区：
文献类型：
--
作者：
Ji, Hanlee;Kumm, Jochen;Davis, Ronald W.
基因组不稳定性是结直肠癌和其他癌症肿瘤发展的一个主要特征。特定的基因组不稳定事件，如染色体缺失和基因拷贝数的其他变化，作为生物学相关的预后生物标记物具有潜在的实用价值。例如，染色体臂18q上的基因组缺失是结直肠癌行为的指标，并可能作为预后指标。采用一种名为分子倒置探针的新基因组技术，该技术可以确定基因复制改变，如基因组缺失，我们设计了一组探针，以询问数百个单独的外显子，覆盖所有染色体臂。此外，>；100探针设计在染色体18q上的微卫星标记附近。我们分析了一组结直肠癌细胞系和原发结直肠癌样本的基因复制改变和外显子缺失突变。基于聚类分析，我们区分了结直肠癌细胞系基因组不稳定的不同类别。我们对原发肿瘤的分析发现了几种不同类型的结直肠癌，每种类型都有特定的18q缺失和特定基因的缺失突变模式。这一发现具有潜在的临床意义，因为18q杂合性丢失事件可作为11期结直肠癌辅助治疗的潜在指标。
Genomic instability is a major feature of neoplastic development in colorectal carcinoma and other cancers. Specific genomic instability events, such as deletions in chromosomes and other alterations in gene copy number, have potential utility as biologically relevant prognostic biomarkers. For example, genomic deletions on chromosome arm 18q are an indicator of colorectal carcinoma behavior and potentially useful as a prognostic indicator. Adapting a novel genomic technology called molecular inversion probes which can determine gene copy alterations, such as genomic deletions, we designed a set of probes to interrogate several hundred individual exons of > 200 cancer genes with an overall distribution covering all chromosome arms. In addition, > 100 probes were designed in close proximity of microsatellite markers on chromosome arm 18q. We analyzed a set of colorectal carcinoma cell lines and primary colorectal tumor samples for gene copy alterations and deletion mutations in exons. Based on clustering analysis, we distinguished the different categories of genomic instability among the colorectal cancer cell lines. Our analysis of primary tumors uncovered several distinct categories of colorectal carcinoma, each with specific patterns of 18q deletions and deletion mutations in specific genes. This finding has potential clinical ramifications given the application of 18q loss of heterozygosity events as a potential indicator for adjuvant treatment in stage 11 colorectal carcinoma.