Search tips
Search criteria 


Logo of bmcprocBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Proceedings
BMC Proc. 2012; 6(Suppl 6): P50.
Published online 2012 October 1. doi:  10.1186/1753-6561-6-S6-P50
PMCID: PMC3467714

Structural effect of P278A mutation conferring breast cancer susceptibility in the p53 DNA-binding core domain

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 [1]. 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 [2]. We have analyzed the genetic variation that may alter the expression and function of the TP53 gene using the sequence-homology-based SIFT tool [3] and a structure-based approach using the PolyPhen-2 server [4]. 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. doi: 10.1016/j.molonc.2010.04.011. [PubMed] [Cross Ref]
  • 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. [PMC free article] [PubMed]
  • 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. doi: 10.1038/nprot.2009.86. [PubMed] [Cross Ref]
  • 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. doi: 10.1038/nmeth0410-248. [PMC free article] [PubMed] [Cross Ref]

Articles from BMC Proceedings are provided here courtesy of BioMed Central