DNA methylation of the dihydropyrimidinase DPYS gene promoter in breast tumors with different response to neoadjuvant chemotherapy

Abstract

Within a genome-wide study, we have identified abnormal methylation of the dihydropyrimidinase DPYS gene promoter in breast cancer (BC). Since dihydropyrimidinase is involved in the catabolism of pyrimidine antagonists, the role of DPYS methylation in determining the sensitivity of tumors to such drugs is of interest. Detailed analysis of DPYS methylation in 29 biopsy samples of the LumB BC subtype obtained before neoadjuvant chemotherapy (NACT) with pyrimidine antagonists discovered that tumors with methylated DPYS promoter are more sensitive to NACT than tumors with unmethylated DPYS (AUC=0.87). Our results indicate the advisability of including pyrimidine antagonists in the LumB BC NACT regimens for patients whose tumor biopsy samples taken before treatment demonstrate hypermethylation of the DPYS promoter.