EVIDENCE THAT METACENTRIC AND SUBMETACENTRIC CHROMOSOMES IN CANINE TUMORS CAN RESULT FROM TELOMERIC FUSIONS

We have hypothesized that metacentric and sub-metacentric chromosomes frequently observed in malignant canine tumors are a result of telomer ic fusions. Therefore cells from a canine mammary pleomorphic adenoma were transformed with a plasmid containing the SV40 'early region', kn own to cause telomeric associations. Compared with nontransformed aden oma cells, the cells had a higher proliferative capacity and expressed the large SV40-T-antigen. Karyotype studies showed the conversion fro m a normal to an aberrant karyotype with an increase of bi-armed chrom osomes resulting from fusions of acrocentric chromosomes. In addition, the length of the telomeric repeats (TTAGGG) was determined for an ea rly and a late passage of the transformed cells by Southern hybridizat ion. The length of the telomeric repeats was apparently longer in the 5th than in the 38th passage. In situ hybridization with a telomere-sp ecific DNA revealed interstitial telomeric repeats in the bi-armed chr omosomes. We have concluded that these findings reflect the clonal exp ansion of head-to-head-telomeric fusions of canine acrocentric chromos omes leading to dicentric chromosomes with a very short distance betwe en the two centromeres. Our results support the idea that the apparent centric fusions that have been described in some canine tumors may in fact be the cytogenetic products of head-to-head-telomeric fusions.