IDENTIFICATION OF ADDITIONAL COMPLEMENTATION GROUPS THAT REGULATE GENOMIC INSTABILITY

By somatic cell hybridization, amplification has been found to be a re cessive genetic trait in three tumor cell lines examined. Studies with transgenic mice have shown that amplification frequency can be altere d by a lack of wild-type TP53 (p53) activity. Other factors may regula te this phenotype in tumor cell lines possessing both wild-type p53 ac tivity and amplification ability. Complementation analysis of somatic cell hybrids was performed to delineate groups of tumor cell lines tha t share a common defect that modulates the ability to amplify. The amp lification frequencies of three normal fibroblast X tumor hybrids were suppressed 10-100-fold from parental tumor values, extending the obse rvation that amplification is a recessive genetic characteristic in th ese cell lines. Analysis of tumor X tumor hybrids revealed at least tw o complementation groups. Defects in these groups differed from TP53 a nd implicate multiple variables in the regulation of gene amplificatio n. (C) 1997 Wiley-Liss, Inc.