Identification of novel deletion polymorphisms in breast cancer

Breast cancer is the most frequent cancer in females worldwide and it has long been known that multiple genetic rearrangements correlate with complex biology and clinical behavior. In addition, copy number variations (CNVs) of DNA sequences account for a significant proportion of normal phenotypic variation and may have an important role in human pathological variation. In this study, we carried out a high-density oligonucleotide array comparative genomic hybridization (CGH) analyses in a series of breast cancer cell lines to identify novel homozygous deletion loci. The results were confirmed by quantitative PCR (Q-PCR) and 4 genes, the REV1L, ZNF14, NPAS1 and APOBEC3B genes, were selected. Analyses of 30 microdissected human breast tumors and paired normal mammary tissue samples indicated that these homozygous deletions are small-scale deletion polymorphisms. The variation in copy number at the loci of the 4 genes in blood-derived DNA demonstrated the frequency of deletions including homozygous deletions and single copy variants to be higher in breast cancer patients than healthy females. Notably, the homozygous deletion of APOBEC3B involved part of exon 5 and seemed to be cancer-specific in some patients, indicating that this is a functionally important structural variant. These copy number changes may play an important role in breast cancer and array-CGH analyses can thus be expected to provide new insight into the genetic background of breast cancer.