CORRESPONDENCE

Re: Sit, DNA, Sit: Cancer Genetics Going to the Dogs

Nicola Reimann, Ingo Nolte, Sabine Bartnitzke, Jörn Bullerdiek

Affiliations of authors: N. Reimann, S. Bartnitzke, J. Bullerdiek, Center for Human Genetics and Genetic Counselling, University of Bremen, Germany; I. Nolte, Clinic for Small Animals, School of Veterinary Medicine, Hanover, Germany.

Correspondence to: J. Bullerdiek, Ph.D., Center for Human Genetics and Genetic Counselling, University of Bremen, Leobener Str. ZHG, D-28359 Bremen, Germany (e-mail: bullerd{at}uni-bremen.de).

In a recent issue of the Journal, Kuska stressed that dogs with spontaneously developing tumors provide an excellent opportunity to study many aspects of cancer from etiology to treatment, making it reasonable that ". . . human genetics—including cancer genetics—will go to the dogs in the 21st century" (1). As the most convincing argument, dogs share the same environment as their owners, and the morphology of many canine neoplasms closely resembles human tumors. Nevertheless, more than 30 500 karyotypically abnormal human neoplasms are listed in the "Catalog of Chromosome Aberrations in Cancer" (2), whereas canine tumor cytogenetics is still in its infancy.

This report is based on cytogenetic investigations of 270 canine solid tumors of different histologic types. As for their site of origin, breast tumors were the largest group of cases followed by tumors of the oral cavity and skin tumors. In 62 (23%) tumors, clonal aberrations were found. Karyotypes were described by Reimann et al. (3). Generally akin to human tumors, clonal aberrations were found in benign as well as in malignant tumors. Of interest in both groups, mesenchymal tumors (sarcomas and lipomas) showed a higher incidence of clonal abnormalities than epithelial neoplasms. This finding is also comparable to human solid tumors (2).

As for the type of aberrations, numeric changes and chromosome fusions predominated. Fig. 1Go summarizes all aberrations that were clearly identified. Obviously, chromosomes 2 and X are among the preferred targets of chromosomal changes. While chromosome 2 is predominantly affected by numeric changes, the X chromosome is a frequent target of structural aberrations. Moreover, chromosomes 1, 19, and 25 are preferentially involved in chromosome fusions. Translocations were rarely found in canine tumors, whereas they are frequent karyotypic changes in human tumors. In contrast, fusions of whole chromosomes, most likely due to telomeric associations (or fusions) (4), are much more frequent in canine than in human tumors. In the "Catalog of Chromosome Aberrations in Cancer," 70 of 30 541 (0.23%) human tumors with telomeric associations are listed (2), whereas in our series of canine tumors, the corresponding figure is 20 of 62 (32.3%). However, this difference does not necessarily indicate that they evolve with a different frequency; the difference might be because dicentrics have a limited life span unless one centromere becomes inactivated. The stability of telomeric associations may depend on the type of fusion, with head-to-head fusions of acrocentric chromosomes having the highest stability. Since the features of the canine karyotype (76 acrocentric autosomes), clonal propagation of these changes may thus occur with a much higher probability than in human cells.



View larger version (53K):
[in this window]
[in a new window]
 
Fig. 1. Schematic representation of the observed clonal abnormalities in 270 cytogenetically investigated canine solid tumors. The numbers in the boxes beside the chromosomes indicate the chromosome regions. Colored lines indicate the chromosomes affected by the aberrations. Red lines = numeric changes; green lines = chromosomes involved in telomeric association; and black lines = structural changes with exception of the telomeric associations.

 
This study clearly shows that the cytogenetic situation for canine and human tumors is comparable. The results already allow for a clustering of aberrations to specific chromosomes. Comparative cytogenetics will help to delineate genomic regions commonly affected by aberrations in both species and thus will faciliate the identification of relevant molecular changes.

REFERENCES

1 Kuska B. Sit, DNA, sit: cancer genetics going to the dogs [news]. J Natl Cancer Inst 1999;91:204-6.[Free Full Text]

2 Catalog of chromosome aberrations in cancer [catalog on CD-ROM]. Mitelman F. Willey-Liss, producers. Version 1. New York: Willey-Liss; 1998.

3 Reimann N, Bartnitzke S, Bullerdiek J, Schmitz U, Rogalla P, Nolte I, et al. An extended nomenclature of the canine karyotype. Cytogenet Cell Genet 1996;73: 140-4.[Medline]

4 Reimann N, Rogalla P, Kazmierczak B, Bonk U, Nolte I, Grzonka T, et al. Evidence that metacentric and submetacentric chromosomes in canine tumors can result from telomeric fusions. Cytogenet Cell Genet 1994;67:81-5.[Medline]


This article has been cited by other articles in HighWire Press-hosted journals:


             
Copyright © 1999 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement