의생명시스템학부

Cancer is a very complex, heterogeneous disease caused by accumulation of multiple genetic and epigenetic alterations in a stepwise fashion. Recurrent genomic amplification is one of critical genetic event promoting oncogene activation during tumor progression. Furthermore, next-generation sequencing (NGS) has recently revealed that many epigenetic regulators, especially histone modifying enzymes, are frequently altered by gene amplification or mutation across multiple cancer types. Using the cancer genome data from patients with breast cancer, we have found molecular signatures associated with cancer stem cell-like features and resistance to conventional therapies in different subtypes of breast cancer. Our findings have demonstrated that histone methyltransferases, NSD3 and SMYD3, which are activated by gene amplification in breast cancer, play a crucial role in cancer initiation and metastatic progression. Furthermore, the gene amplifications of RBP2 and SMYD3, the demethylase and methyltransferase for histone H3K4, are associated with resistance to endocrine therapy in estrogen receptor (ER)-positive breast cancer, while the gene amplification of MEL-18 at 17q12 region indicates the susceptibility to anti-HER2 drugs in HER2-positive breast cancer. Taken together, these findings suggest the epigenetic modifiers with recurrent gene amplification as potential biomarkers for predicting the prognosis and therapeutic response and as novel actionable molecular targets to overcome resistance to anti-cancer drugs in human breast cancer.