Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression
Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression
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DOI：
10.1136/gut.2007.143065
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发表时间：
2009-01-01
期刊：
影响因子：
24.5
通讯作者：
Meijer, G. A.
中科院分区：
文献类型：
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作者：
Carvalho, B.;Postma, C.;Meijer, G. A.
目的：本研究旨在通过测量20q增益对该扩增子基因mRNA表达的影响，确定在20q上参与结直肠腺瘤向癌进展的癌基因。方法：采用阵列CGH（比较基因组杂交）技术，对34例未进展性结直肠腺瘤、41例进展性腺瘤（即有癌灶的腺瘤）和33例腺癌的20q基因拷贝数变化进行分割。此外，通过微阵列分析，对37例腺瘤和31例腺癌中这些片段的基因表达进行了强有力的分析。组织微阵列免疫组化检测蛋白表达。结果：定位于20q的基因C20orf24、AURKA、RNPC1、TH1L、ADRM1、C20orf20和TCFL5在癌中与腺瘤相比，由于20q拷贝数的增加而显著过表达。结论：该方法揭示了C20orf24、AURKA、RNPC1、TH1L、ADRM1、C20orf20和TCFL5基因在染色体不稳定性相关腺瘤的癌进展中起重要作用。因此，这些基因可能作为结直肠癌的高度特异性生物标志物，具有潜在的临床应用价值。
Objective: This study aimed to identify the oncogenes at 20q involved in colorectal adenoma to carcinoma progression by measuring the effect of 20q gain on mRNA expression of genes in this amplicon.Methods: Segmentation of DNA copy number changes on 20q was performed by array CGH (comparative genomic hybridisation) in 34 non-progressed colorectal adenomas, 41 progressed adenomas (ie, adenomas that present a focus of cancer) and 33 adenocarcinomas. Moreover, a robust analysis of altered expression of genes in these segments was performed by microarray analysis in 37 adenomas and 31 adenocarcinomas. Protein expression was evaluated by immunohistochemistry on tissue microarrays.Results: The genes C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5, mapping at 20q, were significantly overexpressed in carcinomas compared with adenomas as a consequence of copy number gain of 20q.Conclusion: This approach revealed C20orf24, AURKA, RNPC1, TH1L, ADRM1, C20orf20 and TCFL5 genes to be important in chromosomal instability-related adenoma to carcinoma progression. These genes therefore may serve as highly specific biomarkers for colorectal cancer with potential clinical applications.