Mutations in Human Interferon alpha 2b Gene and Potential as Risk Factor Associated with Female Breast Cancer

作者：Ahmed Fayyaz; Mahmood Nasir^*; Shahid Saman; Hussain Zahid; Ahmed Ishtiaq; Jalal Amir; Ijaz Bushra; Shahid Abubaker; Mujtaba Ghulam; Mustafa Tanveer

来源：Cancer Biotherapy and Radiopharmaceuticals, 2016, 31(6): 199-208.

DOI：10.1089/cbr.2016.2046

• breast cancer
• interferon
• mutation
• protein variants

The current study explored the potential links between breast cancer and human interferon alpha-2b (hIFN alpha-2b) gene mutations. The hIFN alpha-2b gene was amplified from breast cancer tumor tissue samples (N = 60) by polymerase chain reaction (PCR) and the products were subjected to gene sequencing. A total of 38 (63.3%) samples showed positive PCR amplification results. Several of these also exhibited frequent alterations (mutations) after 400 bp and, in particular, adenine was replaced by other bases. A total of 19 selected mutated amino acids were analyzed for local/general fold pattern changes. Human IFN alpha-2b receptor (IFNAR): ligand (hIFN alpha-2b protein) interactions through a Z-DOCK (3.0.2) server were also evaluated to assess the binding patterns of each ligand to receptor to induce Janus-Kinase-signal transducer and activator of transcription antiproliferative signal transduction pathway inside the cancer cells. Certain local structural and conformational changes were predicted to be induced by mutations in the ligand. The variant models of the hIFN alpha-2b displayed structural and conformational changes that signified that changes to hIFN alpha-2b may be a risk factor in addition to other known factors associated with onset/progression of female breast carcinoma. It was hoped that others might build upon the research in this study evaluating protein structural models with mutations and their consequent interactions with receptors in the development of potent immune therapeutic drugs for breast cancer that are based on recombinant hIFN alpha-2b.

• 出版日期2016-8