Genome-wide copy number analysis in primary breast cancer

Carcinogenesis is considered to be a multistep process that may involve cumulative genomic alterations. Loss of chromosomal material would inactivate tumor suppressor genes and gain of chromosomal material has the potential to activate tumor-promoting genes.

Recent intensive studies by array comparative genomic hybridization (aCGH) have demonstrated frequent alterations in multiple regions of the genome. This suggests that these regions contain a variety of oncogenes and tumor suppressor genes associated with breast cancer development. The patterns of copy number variations (CNVs) have been suggested to be associated with breast cancer subtypes, indicating the importance of genomic instability in the development of breast cancer.

To further clarify the complexity of gene alterations, one approach is to employ a CNV-targeted platform that harbors a large number of direct CNV markers located in the repeat-rich unstable regions of the human genome. Next generation sequencing is another approach to overcome the limitations of aCGH such as the repeat-rich regions. Genomic analysis should be combined with expression analysis to elucidate individual genes relevant to breast cancer development and progression. The elucidation of the functions of the affected genes would lead to identification of new molecular targets for breast cancer eradication.