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

Beevi SS, Anbrasu K, Kannepalli KK, Verma VK, Pillarisetti RR, Madigubba S, Darapuneni RC, Bollineni BR

Pdf Page Numbers :- 186-193

Syed Sultan Beevi^1,*, Kavitha Anbrasu¹, Krishna Kiran Kannepalli^2,3, Vinod Kumar Verma^1,*, Raghu Ram Pillarisetti⁴, Sailaja Madigubba⁵, Radhika Chowdary Darapuneni⁵, and Bhaskar Rao Bollineni¹

¹KIMS Foundation and Research Centre, KIMS Hospital, Minister Road, Secunderabad 500003, Telangana, India

²Department of Surgical Oncology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 500003, Telangana, India

³American Oncology Institute, Citizens Specialty Hospital, Hyderabad 500019, India

⁴Ushalakshmi Centre for Breast Disease, Krishna Institute of Medical Sciences, Minister Road, Secunderabad 500003, Telangana, India

⁵Diagnostics Division, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, Telangana, India

*Corresponding authors: Dr. Syed Sultan Beevi, PhD., KIMS Foundation and Research Centre, KIMS Hospitals, 1-8-31/1, Minister Road, Secunderabad 500003, Telangana, India. Email: drsyedsultan.b@kfrc.co.in; Dr. Vinod Kumar Verma, PhD., KIMS Foundation and Research Centre, KIMS Hospitals, 1-8-31/1, Minister Road, Secunderabad 500003, Telangana, India. Email: drvinod.v@kfrc.co.in

Received 14 April 2023; Revised 14 June 2023; Accepted 21 June 2023; Published 30 June 2023

Citation: Beevi SS, Anbrasu K, Kannepalli KK, Verma VK, Pillarisetti RR, Madigubba S, Darapuneni RC, Bollineni BR. Impact of promoter region mutations of Pim-1 on c-Myc expression as well as survival in patients with breast cancer. J Med Sci Res. 2023; 11(3):186-193. DOI: http://dx.doi.org/10.17727/JMSR.2023/11-35

Copyright: © 2023 Beevi SS et al. Published by KIMS Foundation and Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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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.

Keywords: Pim-1 promoter; c-Myc; survival rate; transversion mutation; constitutive gene