In silico SNP analysis of the breast cancer antigen NY-BR-1.

Zeynep Kosaloglu,Dirk Jäger,Marc Zapatka,Inka Zörnig,Zhiqin Huang,Julia Bitzer,Andreas Schneeweiss,Niels Halama

doi:10.1186/s12885-016-2924-7

Abstract

BackgroundBreast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. Although early stage breast cancer can be effectively treated, there are limited numbers of treatment options available for patients with advanced and metastatic disease. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue. The biological function and regulation of NY-BR-1 is up to date unknown.MethodsWe performed an in silico analysis on the genetic variations of the NY-BR-1 gene using data available in public SNP databases and the tools SIFT, Polyphen and Provean to find possible functional SNPs. Additionally, we considered the allele frequency of the found damaging SNPs and also analyzed data from an in-house sequencing project of 55 breast cancer samples for recurring SNPs, recorded in dbSNP.ResultsOver 2800 SNPs are recorded in the dbSNP and NHLBI ESP databases for the NY-BR-1 gene. Of these, 65 (2.07%) are synonymous SNPs, 191 (6.09%) are non-synoymous SNPs, and 2430 (77.48%) are noncoding intronic SNPs. As a result, 69 non-synoymous SNPs were predicted to be damaging by at least two, and 16 SNPs were predicted as damaging by all three of the used tools. The SNPs rs200639888, rs367841401 and rs377750885 were categorized as highly damaging by all three tools. Eight damaging SNPs are located in the ankyrin repeat domain (ANK), a domain known for its frequent involvement in protein-protein interactions. No distinctive features could be observed in the allele frequency of the analyzed SNPs.ConclusionConsidering these results we expect to gain more insights into the variations of the NY-BR-1 gene and their possible impact on giving rise to splice variants and therefore influence the function of NY-BR-1 in healthy tissue as well as in breast cancer.

Highlights

Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women
We identified a small number of non- synonymous SNPs (nsSNP) which seem to affect the protein function of NY-BR-1
Single Nucleotide Polymorphism (SNP) Mining In the Ensembl BioMart database 2898 SNPs are recorded for the ANKRD30A transcript ENST00000611781. 2880 of these were imported from dbSNP and 18 from NHLBI Exome Sequencing Project (ESP). 1832 SNPs have been validated by independent submissions or frequency/genotype data

Summary

Introduction

Breast cancer is one of the most common malignancies with increasing incidences every year and a leading cause of death among women. The novel breast cancer associated antigen NY-BR-1 was identified by SEREX analysis and is expressed in the majority (>70%) of breast tumors as well as metastases, in normal breast tissue, in testis and occasionally in prostate tissue. A novel breast cancer differentiation antigen, designated as New. York-Breast-1 (NY-BR-1), was identified by a serological cloning strategy (SEREX) [1, 2] and could be a possible target for immunotherapy for breast cancer patients [3]. Computational analyses have identified NY-BR-1 as being a potential transcription factor, the functional aspects of this 158.9 kDa protein are still unknown.

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