Analysis of the dynamic aberrant landscape of DNA methylation and gene expression during arsenic-induced cell transformation.

Inorganic arsenic is a well-known carcinogen associated with several types of cancer, but the mechanisms involved in arsenic-induced carcinogenesis are not fully understood. Recent evidence points to epigenetic dysregulation as an important mechanism in this process; however, the effects of epigenetic alterations in gene expression have not been explored in depth. Using microarray data and applying a multivariate clustering analysis in a Gaussian mixture model, we describe the alterations in DNA methylation around the promoter region and the impact on gene expression in HaCaT cells during the transformation process caused by chronic exposure to arsenic. Using this clustering approach, the genes were grouped according to their methylation and expression status in the epigenetic landscape, and the changes that occurred during the cellular transformation were identified adequately. Thus, we present a valuable method for identifying epigenomic dysregulation.

Analysis of canine transmissible veneral tumor genotypes using the D-loop region of mitochondrial DNA.

Canine transmissible venereal tumor (CTVT) is the only neoplasm that can be spread among dogs through cell transplantation. Therefore, this tumor does not originate from host cell transformation. Although CTVT has a monophyletic origin, several studies have shown the presence of genetic diversity which was probably acquired after the development of its original clone. To investigate the genetic diversity of CTVT in Mexico and its relation with CTVTs disseminated worldwide, we sequenced a fragment of mitochondrial DNA in 50 tumor samples and matched blood samples from dog hosts from Mexico. We found ten new haplotypes in tumor samples, which were all distinct from their matched host. The TVT1 haplotype was the most frequent in our samples, suggesting that it could be the origin of the others. We found that haplotypes in Mexico and other countries are distributed in two well-defined clusters. Our data also suggest a close relationship among American haplotypes (Mexico, USA, Chile and Brazil). Interestingly, these American haplotypes were also closely related to Asian haplotypes. Taking into account the estimated timing of the origin of CTVT, we propose that CTVT might have originated in Asia; consequently, haplotypes currently present in America could descend from Asiatic lineages.