2Department of Medical Genetics, Eskisehir Osmangazi University Faculty of Medicine, Eskişehir-Turkey
3Department of Molecular Biology and Genetic, Bilecik Seyh Edebali University Faculty of Art&Science, Bilecik-Turkey
4Department of Molecular Pathology, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir-Turkey
5Department of Biostatistics and Medical Informatics, Kocaeli University Faculty of Medicine, Kocaeli-Turkey DOI : 10.5505/tjo.2019.2017 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.