Supported by: F.L.M. de Groen was supported by a VUMC-CCA grant.
Gene-dosage dependent overexpression at the 13q amplicon identifies DIS3 as candidate oncogene in colorectal cancer progression
Article first published online: 29 JAN 2014
Copyright © 2014 Wiley Periodicals, Inc.
Genes, Chromosomes and Cancer
Volume 53, Issue 4, pages 339–348, April 2014
How to Cite
de Groen, F. L.M., Krijgsman, O., Tijssen, M., Vriend, L. E.M., Ylstra, B., Hooijberg, E., Meijer, G. A., Steenbergen, R. D.M. and Carvalho, B. (2014), Gene-dosage dependent overexpression at the 13q amplicon identifies DIS3 as candidate oncogene in colorectal cancer progression. Genes Chromosom. Cancer, 53: 339–348. doi: 10.1002/gcc.22144
- Issue published online: 14 FEB 2014
- Article first published online: 29 JAN 2014
- Manuscript Accepted: 27 DEC 2013
- Manuscript Revised: 23 DEC 2013
- Manuscript Received: 4 OCT 2013
Colorectal cancer (CRC) development is in most cases marked by the accumulation of genomic alterations including gain of the entire q-arm of chromosome 13. This aberration occurs in 40%–60% of all CRC and is associated with progression from adenoma to carcinoma. To date, little is known about the effect of the 13q amplicon on the expression of the therein located genes and their functional relevance. We therefore aimed to identify candidate genes at the 13q amplicon that contribute to colorectal adenoma to carcinoma progression in a gene dosage-dependent manner. Integrative analysis of whole genome expression and DNA copy number signatures resulted in the identification of 36 genes on 13q of which significant overexpression in carcinomas compared with adenomas was linked to a copy number gain. Five genes showing high levels of overexpression in carcinomas versus adenomas were further tested by quantitative reverse transcription-PCR in two independent sample sets of colorectal tumors (n = 40 and n = 47). DIS3 and LRCH1 revealed significant overexpression in carcinomas compared with adenomas in a 13q gain dependent manner. Silencing of DIS3 affected important tumorigenic characteristics such as viability, migration, and invasion. In conclusion, significant overexpression of DIS3 and LRCH1 associated with adenoma to carcinoma progression is linked to the CRC specific gain of 13q. The functional relevance of this copy number aberration was corroborated for DIS3, thereby identifying this gene as novel candidate oncogene contributing to the 13q-driven adenoma to carcinoma progression. © 2014 Wiley Periodicals, Inc.