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

Abstract

OBJECTIVEBreast cancer (BC) is a heterogeneous malignancy and differs widely among different patients. The aimof 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.METHODSFormalin-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 FFPEtumor tissues, and Methylation-sensitive high resolution melting (MS-HRM) analysis were performedfor RASSF1A/APC genes methylation status.RESULTSHER2 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 tumorgrade (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 betweenAPC methylation and TOP2A aberration. APC gene methylation was significantly more frequent intumors with TOP2A aberration (p=0.026).CONCLUSIONOur results suggested that APC gene promoter hypermethylation was associated with TOP2A geneaberrations 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 theHER2 gene amplification seen in BC.