title: 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.
authors: a Department of Biotechnology , Dr. M.G.R. Educational and Research Institute (University) , Maduravoyal, Chennai 600 095 , India.
authors: N
authors: N
authors: Sudhakar
authors: b Medical Biotechnology Division, School of Biosciences and Technology (SBST) , VIT University , Vellore 632 014 , India.
authors: C George
authors: CG
authors: Priya Doss
authors: b Medical Biotechnology Division, School of Biosciences and Technology (SBST) , VIT University , Vellore 632 014 , India.
authors: D
authors: D
authors: Thirumal Kumar
authors: c Department of Bioinformatics, School of Computer and Information Sciences , Galgotias University , Greater Noida , India.
authors: Chiranjib
authors: C
authors: Chakraborty
authors: a Department of Biotechnology , Dr. M.G.R. Educational and Research Institute (University) , Maduravoyal, Chennai 600 095 , India.
authors: Kushi
authors: K
authors: Anand
authors: a Department of Biotechnology , Dr. M.G.R. Educational and Research Institute (University) , Maduravoyal, Chennai 600 095 , India.
authors: M
authors: M
authors: Suresh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005091:Exons / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human
keywords: PIK3CA; South India; breast cancer; in silico prediction methods; molecular dynamics simulation analysis; somatic mutations