Spontaneous mutation rates in cloned murine tumors do not correlate with metastatic potential, whereas the prevalence of karyotypic abnormalities in the parental tumors does

Abstract

We tested the hypothesis that highly malignant cell lines are genomically more unstable than their less malignant counterparts, and that this instability is more pronounced in clones than in cell lines. We compared MDAY-D2 to its non-metastatic variant, D36W25, with regard to (I) the rate of development of ouabain resistance within parallel clones and (2) the prevalence of G-banded karyotypic abnormalities. We detected no significant difference between the spontaneous mutation rates for ouabain resistance. However, the MDAY-D2 cell line possessed both a higher prevalence and greater diversity of chromosomal abnormalities. One possible explanation for these seemingly inconsistent results is that genomic instability may remain essentially constant throughout tumor progression, whereas an accumulation of genetic changes may be responsible for the observed increased prevalence of abnormalities and the development of selective survival advantages during progression.