Deciphering the impact of somatic mutations in exon 20 and exon 9 of PIK3CA gene in breast tumors among Indian women through molecular dynamics approach

Abstract

We examined 25 breast tumor samples for somatic mutations in exon 20 and exon 9 of PIK3CA gene in South Indian population. Genomic DNA was isolated and amplified for PIK3CA gene, followed by direct sequencing of purified polymerase chain reaction products. We identified PI3K3CA mutations in 5 of 25 (20%), including four of the mutations in p.H1047R and one in p.H1047L. Nucleotide base substitution A to G (c.3140A > G) and A to T (c.3140A > T) results in p.H1047R and p.H1047L mutation in exon 20 of PIK3CA gene. We did not observe any mutation in exon 9 of PIK3CA gene. Furthermore, we investigated the effect of mutations on protein structure and function by the combination of sequence and structure-based in silico prediction methods. This determined the underlying relationship between the mutation and its phenotypic effects. Next step, we complemented by molecular dynamics simulation analysis (30 ns) of native and mutant structures that measured the effect of mutation on protein structure. The obtained results support that the application of computational methods helps predict the biological significance of mutations.

Keywords:

• PIK3CA
• breast cancer
• somatic mutations
• South India
• in silico prediction methods
• molecular dynamics simulation analysis

Acknowledgments

We sincerely thank Dr. M.G.R. Educational and Research Institute, VIT University, and Galgotia University for providing the laboratory facility and support for conducting the study. We acknowledge Dr. Venil N Sumantran, Visiting Faculty, Dr. M.G.R. E & R.I for her valuable guidance and critical review of the manuscript.

Additional information

Funding

We profoundly acknowledge the grant received from Science and Engineering Research Board (SERB), Govt. of India Project File [SR/FT/LS-140/2010].