A recurring pattern of chromosomal aberrations in mammary gland tumors of MMTV-cmyc transgenic mice

Mice carrying the MMTV-cmyc transgene develop mammary tumors at 9 to 12 mon ths of age, Little is known about karyotypic changes in this model of human breast cancer. We have developed and applied molecular cytogenetic techniq ues to study chromosomal aberrations that occur in these tumors, namely, co mparative genomic hybridization and spectral karyotyping. Cell lines from e ight tumors were established and analyzed, four of which carried a heterozy gous p53 mutation. All of the tumor cell lines revealed increases in ploidy and/or multiple numerical and structural chromosomal aberrations. No consi stent differences were observed between cmyclp53(+/+) and cmyclp53(+/-) tum ors, suggesting that cmyc induces karyotype instability independent of p53 status. Loss of whole chromosome (Chr) 4 was detected in five of the eight tumors. Parts of Chr 4 are syntenic to human 1p31-p36, a region that is als o deleted in human breast carcinomas, Four tumors carried translocations in volving the distal portion of Chr I I (syntenic to human chromosome arm 17q ), including two translocations T(X; I I), with cytogenetically identical b reakpoints. We compare the pattern of chromosomal aberrations with human br east cancers, find similarities in several syntenic regions, and discuss th e potential of an interspecies cytogenetic map of chromosomal gains and los ses. Published 1999 Wiley-Liss, Inc.dagger.