Impact of promoter region mutations of Pim-1 on c-Myc expression as well as survival in patients with breast cancer

Abstract

Purpose: Breast cancer accounts for most cancer-related deaths in women with over 2.3 million new breast cancer cases diagnosed every year worldwide. Pim kinases are oncogenic proteins that play important role in various cancers. Pim-1 contains 1.7 kb promoter region without any transcriptional regulation, which is a characteristic feature of a housekeeping or constitutive promoter. This study was carried out to ascertain potential mutations in the promoter region of Pim-1 in breast cancer and also to comprehend the effect of mutations on c-Myc expression as well as on patients’ survival. Methods: Ninety-six Indian subjects with a first diagnosis of breast cancer who underwent surgery at our hospital were recruited in this study. Genomic DNA was isolated from whole blood, amplified and sequenced to identify potential mutations at the promoter region of Pim-1. FFPE sections were used to determine the c-Mycexpression in all the studied groups. Results: We observed a transversion (C>A at –502) and a deletion (–754Cdel) mutation in the promoter region with negligible association with tumor biology and c-Myc expression. Positive c-Myc expression was noted in almost 50% of the studied population with absolute nuclear staining or both cytoplasmic/nuclear staining. As per survival analysis, promoter region mutations did not modulate the patients’ survival, but patients with negative c-Myc expression had better disease-free survival compared with positive c-Myc expression. Conclusion: Our findings identified the presence of mutation in the promoter region of Pim-1 with negligible impact on c-Myc expression in patients with breast cancer.