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

@article{Sudhakar2016DecipheringTI,
  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},
  author={Natarajan Sudhakar and C. George Priya Doss and D. Thirumal Kumar and Chiranjib Chakraborty and Kushi Anand and Manju Suresh},
  journal={Journal of Biomolecular Structure and Dynamics},
  year={2016},
  volume={34},
  pages={29 - 41}
}
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… Expand
Molecular evaluation of PIK3CA gene mutation in breast cancer: determination of frequency, distribution pattern and its association with clinicopathological findings in Indian patients
TLDR
PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non-DCIS tumors; however, none of the differences were significant. Expand
PIK3CA mutations in HER2-positive Breast Cancer Patients; Frequency and Clinicopathological Perspective in Egyptian Patients
TLDR
The PIK3CA mutation frequency in this study is the first report regarding HER2-positive breast cancer patients in Egypt and could be useful in the future as a predictive marker for anti-HER2 therapy. Expand
Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach
TLDR
It is reported that the mere existence of mutant E545K can trigger the function of the protein but may not be as harmful as H1047R, and the latter shows the most deleterious effect that correlates with the previous reported experimental studies. Expand
Mutation distributions and clinical correlations of PIK3CA gene mutations in breast cancer
TLDR
It is reported that PIK3CA mutations which have been localized mostly on exon 9 and 20 hot spots are detected 25–40 % in BCa, which can offer an advantage for choosing the best treatment options for BCa. Expand
Role of E542 and E545 missense mutations of PIK3CA in breast cancer: a comparative computational approach.
TLDR
A large number of mutations observed in PIK3CA have the ability to trigger the different activities of the cell, thereby bypassing the regular cellular cycle and the deleterious effect of these mutations is compared in silico prediction tools. Expand
Clinical-Pathologic Analysis of Breast Cancer With PIK3CA Mutations in Chinese Women
TLDR
A high frequency of somatic PIK3CA mutation was detected in Chinese breast cancer patients, especially in exon 20, and seems to have the potential to be used in target treatment and as an indicator of prognosis. Expand
PIK3CA somatic alterations in invasive breast cancers: different spectrum from Caucasians to Chinese detected by next generation sequencing
TLDR
PIK3CA alterations prevail in Chinese BC patients and have different molecular features compared to that of Caucasians, and precise annotations of Pik3CA genomic alterations of Chinese are provided in the context of application of PIK3 CA inhibitor. Expand
Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach.
  • D. T. Kumar, C. Doss
  • Biology, Medicine
  • Advances in protein chemistry and structural biology
  • 2016
TLDR
Though Wortmannin was found to nullify the effect of H1047R over the protein, further studies are required for designing a better compound as SNPs are major genetic variations observed in disease condition. Expand
Determining the role of missense mutations in the POU domain of HNF1A that reduce the DNA-binding affinity: A computational approach
TLDR
The HNF1A protein was retrieved from public databases and subjected to a three-step computational mutational analysis to identify the underlying mechanism and the MD approach is an important tool for elucidating the impact and affinity of mutations in DNA-protein interactions and understanding their function. Expand
Investigating mutations at the hotspot position of the ERBB2 and screening for the novel lead compound to treat breast cancer - a computational approach.
TLDR
A computational pipeline was developed to identify the mutation position with a highest number of mutations and to screen them for pathogenicity, stability, conservation, and structural changes using PredictSNP, iStable, ConSurf, and GROMACS simulation software respectively and witnessed CID140590176 be a potential lead compound with no toxicity. Expand
...
1
2
3
...

References

SHOWING 1-10 OF 71 REFERENCES
Phosphatidylinositol 3-kinase (PI3KCA) oncogene mutation analysis and gene expression profiling in primary breast cancer patients.
TLDR
PIK3CA mutation is an emerging tumor marker that, in the future, might be used in the process of choosing a treatment and the detection of PI3KCA mutation might have important clinical implications for diagnosis, progression and therapy. Expand
Somatic mutation and gain of copy number of PIK3CA in human breast cancer
TLDR
The frequent and clustered mutations within PIK3CA make it an attractive molecular marker for early detection and a promising therapeutic target in breast cancer. Expand
Mutation of the PIK3CA Gene in Ovarian and Breast Cancer
TLDR
This study is the first direct evidence that PIK3CA is an oncogene in ovarian cancer and greatly extends recent findings in breast cancer. Expand
An Integrated in Silico Approach to Analyze the Involvement of Single Amino Acid Polymorphisms in FANCD1/BRCA2-PALB2 and FANCD1/BRCA2-RAD51 Complex
TLDR
In silico variation analysis of deleterious non-synonymous SNPs at both functional and structural level in the breast cancer and FA susceptibility gene BRCA2/FANCD1 concludes that the identification of disease-related SNPs by in silico methods, in combination with MD approach has the potential to create personalized tools for the diagnosis, prognosis, and treatment of diseases. Expand
p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization
TLDR
Though these methods predict the p.Arg82Leu mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease. Expand
Structural signature of the G719S-T790M double mutation in the EGFR kinase domain and its response to inhibitors
TLDR
Analyzing the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation and docking analysis provides an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance. Expand
Investigating the Structural Impacts of I64T and P311S Mutations in APE1-DNA Complex: A Molecular Dynamics Approach
TLDR
Different parameters such as RMSD, RMSF, salt bridge, H-bonds and SASA applied in Molecular dynamic study reveals that predicted deleterious variants I64T and P311S alters the structure as well as affect the stability of APE1-DNA interacting functions. Expand
A method and server for predicting damaging missense mutations
TLDR
A new method and the corresponding software tool, PolyPhen-2, which is different from the early tool polyPhen1 in the set of predictive features, alignment pipeline, and the method of classification is presented and performance, as presented by its receiver operating characteristic curves, was consistently superior. Expand
PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas
A recent report revealed that phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene is somatically mutated in several types of human cancer, suggesting the mutated PIK3CA gene as an oncogene inExpand
COSMIC (the Catalogue of Somatic Mutations in Cancer): a resource to investigate acquired mutations in human cancer
TLDR
Examination of COSMIC’s data is primarily web-driven, focused on providing mutation range and frequency statistics based upon a choice of gene and/or cancer phenotype, and Graphical views provide easily interpretable summaries of large quantities of data, and export functions can provide precise details of user-selected data. Expand
...
1
2
3
4
5
...