Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression

被引:209
作者
Carvalho, B. [1 ]
Postma, C. [1 ]
Mongera, S. [1 ]
Hopmans, E. [1 ]
Diskin, S. [2 ,3 ,4 ]
van de Wiel, M. A. [1 ,5 ,6 ]
van Criekinge, W. [7 ]
Thas, O. [8 ]
Matthaei, A. [9 ]
Cuesta, M. A. [10 ]
Droste, J. S. Terhaar sive [11 ]
Craanen, M. [11 ]
Schroeck, E. [9 ]
Ylstra, B. [1 ]
Meijer, G. A. [1 ]
机构
[1] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands
[2] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA
[4] Univ Penn, PCBI, Philadelphia, PA 19104 USA
[5] Vrije Univ Amsterdam Med Ctr, Dept Biostat, NL-1081 HV Amsterdam, Netherlands
[6] Free Univ VU, Dept Math, Amsterdam, Netherlands
[7] Univ Ghent, Fac Biosci Engn, Dept Mol Biotechnol, Lab Bioinformat & Computat Genom, B-9000 Ghent, Belgium
[8] Univ Ghent, Dept Appl Math Biometr & Proc Control, B-9000 Ghent, Belgium
[9] Tech Univ Dresden, Med Fac Carl Gustav Carus, Inst Clin Genet, Dresden, Germany
[10] Vrije Univ Amsterdam Med Ctr, Dept Surg, NL-1081 HV Amsterdam, Netherlands
[11] Vrije Univ Amsterdam Med Ctr, Dept Gastroenterol, NL-1081 HV Amsterdam, Netherlands
关键词
COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION PROFILES; CANCER CELL-LINES; COLON-CANCER; COPY NUMBER; CANDIDATE ONCOGENE; MICROARRAY DATA; AURORA KINASE; BREAST-CANCER; IDENTIFICATION;
D O I
10.1136/gut.2007.143065
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
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.
引用
收藏
页码:79 / 89
页数:11
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