Distinct Patterns in the Regulation and Evolution of Human Cancer Genes

Article type: Research Article

Authors: Furney, Simon J.^; | Madden, Stephen F. | Kisiel, Tomasz A. | Higgins, Desmond G. | Lopez-Bigas, Nuria

Affiliations: Research Unit on Biomedical Informatics, Experimental and Health Science Department, Universitat Pompeu Fabra, Barcelona, 08080, Spain | Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland

Note: [] Corresponding author. Tel.: +34 93 3160507; Fax: +34 93 2240875; E-mail: [email protected]

Abstract: Understanding the mechanism of regulation of cancer genes and the constraints on their coding sequences is of fundamental importance in understanding the process of tumour development. Here we test the hypothesis that tumour suppressor genes and proto-oncogenes, due to their involvement in tumourigenesis, have distinct patterns of regulation and coding selective constraints compared to non-cancer genes. Indeed, we found significantly greater conservation in the promoter regions of proto-oncogenes, suggesting that these genes are more tightly regulated, i.e. they are more likely to contain a higher density of cis-regulatory elements. Furthermore, proto-oncogenes appear to be preferentially targeted by microRNAs and have longer 3' UTRs. In addition, proto-oncogene evolution appears to be highly constrained, compared to tumour suppressor genes and non-cancer genes. A number of these trends are confirmed in breast and colon cancer gene sets recently identified by mutational screening.

Keywords: Oncogenes, tumour suppressor genes, gene regulation, sequence conservation, microRNAs, breast cancer, colon cancer

Journal: In Silico Biology, vol. 8, no. 1, pp. 33-46, 2008