Correlation of HER2/TOP2A Gene Aberrations with RASSF1A/APC Gene Methylation Status in High-Risk Breast Cancer

Abstract

OBJECTIVE Breast cancer (BC) is a heterogeneous malignancy and differs widely among different patients. The aim of this study was to investigate the relationship between the HER2/TOP2A gene aberrations and promoter methylation in RASSF1A/APC genes in patients with high-risk BC. METHODS Formalin-fixed paraffin embedded (FFPE) tissue samples from primary breast tumors (n=60) were assessed. HER2/TOP2A aberrations was evaluated using FISH method. DNA was extracted from FFPE tumor tissues, and Methylation-sensitive high resolution melting (MS-HRM) analysis were performed for RASSF1A/APC genes methylation status. RESULTS HER2 amplification and TOP2A aberration were observed in 15/60 (25%) and 18/60 (30%) cases, respectively. According to the statistical analysis, HER2 amplification was associated with higher tumor grade (p=0.001), PR status (p=0.025), and TOP2A aberrations (p=0.004). RASSF1A and APC methylation were 58/60 (96.6%) and 26/60 (43.3%), respectively. There was a significant correlation between APC methylation and TOP2A aberration. APC gene methylation was significantly more frequent in tumors with TOP2A aberration (p=0.026). CONCLUSION Our results suggested that APC gene promoter hypermethylation was associated with TOP2A gene aberrations in patients with high-risk BC. This may be significant for targeted individual therapy. Additionally, it was confirmed that there was significant association of TOP2A gene aberrations with the HER2 gene amplification seen in BC.