Chromosomal changes in aggressive breast cancers with basal-like features

Abstract

Using high-resolution oligonucleotide comparative genomic hybridization arrays, we evaluated chromosomal copy number changes in a series of 16 breast cancers, selected on the basis of highly similar pathologic and molecular features characteristic of the “basal-like” phenotype. Each of these cancers showed numerous gains and losses, reflecting multiple chromosomal rearrangements during the development of these high-grade cancers. Chromosomal losses were particularly prevalent on chromosomal arms 5q, 8p, 9q, 12q, 17p, 19p, and Xq, and gains were commonly seen on chromosomal arms 1q, 8q, and 17q. The regions of high-level amplification (copy number change more than eightfold) on 4q12, 8q23.3, 19p12, and 19q13.2 were particularly remarkable. These regions included candidate oncogenes cKIT, JUND, and AKT2, and immunohistochemistry confirmed that these particular genes were highly expressed in the cancers harboring the specific amplifications. Each of these amplifications was observed only in individual cases, however, and no particular chromosomal alteration appeared to generally characterize this group of cancers. Thus, genomic changes among breast cancers with basal-like features appear to be very heterogeneous. Distinct high-level amplifications may provide new targets for treating some of these cancers, but copy number changes do not reveal a distinctive genomic fingerprint for this proposed class of breast cancers.