Volume 6 Supplement 6
Structural effect of P278A mutation conferring breast cancer susceptibility in the p53 DNA-binding core domain
© Suneetha and Naidu; licensee BioMed Central Ltd. 2012
Published: 1 October 2012
One of the common malignancies faced by women around the world is breast cancer. Risk factors for breast cancer include both genetic and non-genetic. Variants in some of the candidate genes are a common risk factor in breast cancer. These genetic variants associated with breast cancer can be classified as high, moderate or low based on relative risk . Among them, genes that predispose to high risk for breast cancer include TP53, BRCA1, BRCA2, PTEN, STK11 and CDH1. A large number of studies have assessed the prognostic and predictive role of TP53 alterations in breast cancer. It is well known that TP53 is mutated in about 30% of breast cancers . We have analyzed the genetic variation that may alter the expression and function of the TP53 gene using the sequence-homology-based SIFT tool  and a structure-based approach using the PolyPhen-2 server . These two computational approaches showed that rs17849781 (P278A) has a deleterious phenotypic effect conferring to breast cancer. Further, we have analyzed the structural effect of the P278A mutation in the p53 DNA-binding core domain by employing different computational methods.
- Mavaddat N, Antoniou AC, Easton DF, Garcia-Closas M: Genetic susceptibility to breast cancer. Mol Oncol. 2010, 4: 174-191. 10.1016/j.molonc.2010.04.011.View ArticlePubMedGoogle Scholar
- Varna M, Bousquet G, Plassa LF, Bertheau P, Janin A: TP53 status and response to treatment in breast cancers. J Biomed Biotechnol. 2011, 2011: 284584-PubMed CentralView ArticlePubMedGoogle Scholar
- Kumar P, Henikoff S, Ng PC: Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc. 2009, 4: 1073-1081. 10.1038/nprot.2009.86.View ArticlePubMedGoogle Scholar
- Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR: A method and server for predicting damaging missense mutations. Nat Methods. 2010, 7: 248-249. 10.1038/nmeth0410-248.PubMed CentralView ArticlePubMedGoogle Scholar
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