Characterization of heterogeneity in gene expression of human breast cancer

Abstract

Functional and genetical discrimination between normal and cancer is an important subject for targeted therapies for cancer. One of the several ways to find the properties of cancer is the selection of up- or down-regulated genes in cancer compared with normal samples. However, the heterogeneity of individual cancer makes it difficult to find such changed expressions across breast cancer samples. The primary aim of this study is to identify the genes whose expressions varied among breast cancer samples, and uncover which factors contribute to the heterogeneity in gene expression among breast cancers. The main hypothesis is that each breast cancer patient undergoes an individual adaptation process during cancer progression. Under this assumption, the expression heterogeneity across breast cancer samples could be interpreted as not a result of deregulation but an individual adaptation process. To prove the hypothesis, this study identified and characterized the expression heterogeneity observed in normal breast and breast cancer. Comparison of the gene expression profiles from the breast cancer samples with those of the normal breast tissue revealed that the expression heterogeneity observed across breast cancer samples is one of the key signatures that discriminate the cancer. Indeed, these expression signatures were not observed in any other types of cancer. In addition, this study suggests that the expression heterogeneity specific to breast cancer is influenced by three major contributors - cancer origin, cancer development, and ER status. This result can help to explain how each breast cancer undergoes cancer evolution process, which drives its individual cancer development.