The effects of variations in genomic modules on breast cancer phenotype

The primary aim of this study is to present how expression heterogeneity is reflected in biological processes. Wehypothesize that loss of normal regulatory mechanism is related with changed characteristics of a genomic module, whichemerges its own phenotypes as a whole. In breast cancer, receptor status is related to degree of cancer variations. In thisregard, comparing expression data according to receptor status is a valuable process to prove the hypothesis. For thisreason, we investigated differences of genomic modules according to the receptor status. As a result, 4 and 3 genomicmodules, which represent distinct biological processes, were obtained from estrogen receptor (ER)-/ progesterone receptor(PR)-positive double positive (DP) and ER-/PR-negative double negative (DN) breast cancer groups, respectively. Comparing the genomic modules between the groups, we found that there were differences of functional roles, which weremainly caused by DP-exclusive genes. The DP-exclusive genes showed variable expressions in the DN group but not in theDP group, and these expression heterogeneities in the DN group reflected transition of the genomic modules to have moremalignant properties than in the DP group. In addition, the DP-exclusive genes themselves have a higher possibility to beinvolved in oncogenic processes in the DN group. In conclusion, this study suggests that expression heterogeneity of theDP-exclusive genes is not a result of deregulation, but a process that drives emergence of novel traits.This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF2013R1A1A2A10013032)