Distinct patterns in the regulation and evolution of human cancer genes.
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.
Furney
Simon J
SJ
Research Unit on Biomedical Informatics, Experimental and Health Science Department, Universitat Pompeu Fabra, Barcelona, 08080, Spain.
Madden
Stephen F
SF
Kisiel
Tomasz A
TA
Higgins
Desmond G
DG
Lopez-Bigas
Nuria
N
D020413:3' Untranslated Regions; D005075:Biological Evolution; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000502:physiology*
D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas