Comparative analysis of cancer genes in the human and chimpanzee genomes.
BACKGROUND
Cancer is a major medical problem in modern societies. However, the incidence of this disease in non-human primates is very low. To study whether genetic differences between human and chimpanzee could contribute to their distinct cancer susceptibility, we have examined in the chimpanzee genome the orthologous genes of a set of 333 human cancer genes.


RESULTS
This analysis has revealed that all examined human cancer genes are present in chimpanzee, contain intact open reading frames and show a high degree of conservation between both species. However, detailed analysis of this set of genes has shown some differences in genes of special relevance for human cancer. Thus, the chimpanzee gene encoding p53 contains a Pro residue at codon 72, while this codon is polymorphic in humans and can code for Arg or Pro, generating isoforms with different ability to induce apoptosis or interact with p73. Moreover, sequencing of the BRCA1 gene has shown an 8 Kb deletion in the chimpanzee sequence that prematurely truncates the co-regulated NBR2 gene.


CONCLUSIONS
These data suggest that small differences in cancer genes, as those found in tumor suppressor genes, might influence the differences in cancer susceptibility between human and chimpanzee. Nevertheless, further analysis will be required to determine the exact contribution of the genetic changes identified in this study to the different cancer incidence in non-human primates.
Puente
Xose S
XS
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain. xspuente@uniovi.es
Velasco
Gloria
G
Gutiérrez-Fernández
Ana
A
Bertranpetit
Jaume
J
King
Mary-Claire
MC
López-Otín
Carlos
C
D000818:Animals; D003062:Codon / Q000235:genetics; D019295:Computational Biology; D017124:Conserved Sequence; D019398:Genes, BRCA1; D052138:Genes, Neoplasm; D016158:Genes, p53; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D020125:Mutation, Missense; D016366:Open Reading Frames; D002679:Pan troglodytes / Q000235:genetics*; D013045:Species Specificity
D003062:Codon