Carvalho B, Postma C, Mongera S, Hopmans E, Diskin S, van de Wiel M A, van Criekinge W, Thas O, Matthäi A, Cuesta M A, Terhaar Sive Droste J S, Craanen M, Schröck E, Ylstra B, Meijer G A
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Gut. 2009 Jan;58(1):79-89. doi: 10.1136/gut.2007.143065. Epub 2008 Oct 1.
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.
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.
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.
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.
本研究旨在通过测量20号染色体长臂(20q)扩增对该扩增区域内基因mRNA表达的影响,来鉴定参与大肠腺瘤向癌进展过程的位于20q的癌基因。
采用比较基因组杂交芯片技术(array CGH)对34例未进展的大肠腺瘤、41例进展性腺瘤(即存在癌灶的腺瘤)和33例腺癌进行20q上DNA拷贝数变化的分段分析。此外,通过对37例腺瘤和31例腺癌进行芯片分析,对这些区域内基因表达的改变进行了可靠的分析。通过组织芯片免疫组化评估蛋白表达。
由于20q拷贝数增加,位于20q的C20orf24、极光激酶A(AURKA)、核糖核蛋白C1(RNPC1)、TH1L、ADRM1、C20orf20和TCFL5基因在癌组织中与腺瘤相比显著过表达。
该方法揭示了C20orf24、AURKA、RNPC1、TH1L、ADRM1、C20orf20和TCFL5基因在与染色体不稳定相关的腺瘤向癌进展过程中具有重要作用。因此,这些基因可能作为结直肠癌高度特异性的生物标志物,具有潜在的临床应用价值。