Associations between HER2/neu, TOP2A, chromosome 17 copy numbers, and CDH1 and GSTP1 gene promotor hypermethylations of patients with breast cancer

Abstract

Breast cancer is an important public health problem worldwide. The HER2 /neu protooncogene is amplified and overexpressed in approximately 25-30% of invasive breast carcinomas. DNA topoisomerase 2-alpha enzyme controls and alters the topologic states of DNA during transcription. TWIST expression in breast tumors correlate with increased disease recurrence and poor disease-free survival. Steroid receptor genes family members such as the RARβ2 and ESR1 genes are methylated and silenced in a fraction of breast cancer. Method: In this study we analysed retrospective HER2/neu, TOP2A gene and Chromosome17 copy number alterations by fluorescence in situ hybridization (FISH) in primary tumor core biopsies from 100 high-risk primary breast cancer patients (tumors ≥2 cm and/or lenfatic metastase and/or distant metastases and/or under 40 years) . The methylation levels of the TWIST, RARβ2 and ESR1 gene promoters were assessed Methylation Sensitive High Resolution Melting Analysis (MS-HRM). Results: In our study, HER2/neu amplifications were identified in 25% and TOP2A amplifications in 24% and deletions in 6% of patients. HER2/neu and TOP2A amplifications are found to be associated with IDC tumor type and high grade also HER2/neu amplifications is associated with PR(-), TOP2A amplifications is associated with ER(+). TOP2A deletions is associated with ER(-) and PR(-). Polysomy17 was present in 23% and monosomy 12% of patients. TWIST, RARβ2 and ESR1 methylation frequencies were 24%, 90% and 69% respectively. Conclusions:. Our study is important as being the first study that analyzes association between HER2/neu, TOP2A gene copy numbers and TWIST, RARβ2 and ESR1 gene promotor methylation status in Turkish population