<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations
<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with...
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doaj-2afde2f116394cc9ab4044d8ebe7628d2020-11-24T21:15:32ZengBMCMolecular Cancer1476-45982010-05-019111310.1186/1476-4598-9-113<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutationsAmbs StefanFosså Sophie DLandmark-Høyvik HegeShah AnushiPorter-Gill PatriciaKohaar InduHowe Tiffany MArhancet Juan PKaushiva AlpanaEdvardsen HegeFu Yi-PingNaume BjørnBørresen-Dale Anne-LiseKristensen Vessela NProkunina-Olsson Ludmila<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER)<sup>+ </sup>versus ER<sup>- </sup>cancer.</p> <p>Results</p> <p>We found association between SNP rs11249433 and expression of the <it>NOTCH2 </it>gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of <it>NOTCH2 </it>was found to be lowest in tumors with <it>TP53 </it>mutations and highest in <it>TP53 </it>wild-type/ER<sup>+ </sup>tumors (p = 0.0059). In the latter group, the <it>NOTCH2 </it>expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between <it>NOTCH2 </it>expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of <it>NOTCH2</it>, a truncated version of <it>NOTCH2 </it>consisting of only the extracellular domain.</p> <p>Conclusion</p> <p>This is the first study to show that the expression of <it>NOTCH2 </it>differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER<sup>+ </sup>luminal cells in the breast. Therefore, increased expression of <it>NOTCH2 </it>in carriers of rs11249433 may promote development of ER<sup>+ </sup>luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of <it>NOTCH2 </it>expression by rs11249433 and the role of <it>NOTCH2 </it>splicing forms in breast cancer development.</p> http://www.molecular-cancer.com/content/9/1/113 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ambs Stefan Fosså Sophie D Landmark-Høyvik Hege Shah Anushi Porter-Gill Patricia Kohaar Indu Howe Tiffany M Arhancet Juan P Kaushiva Alpana Edvardsen Hege Fu Yi-Ping Naume Bjørn Børresen-Dale Anne-Lise Kristensen Vessela N Prokunina-Olsson Ludmila |
spellingShingle |
Ambs Stefan Fosså Sophie D Landmark-Høyvik Hege Shah Anushi Porter-Gill Patricia Kohaar Indu Howe Tiffany M Arhancet Juan P Kaushiva Alpana Edvardsen Hege Fu Yi-Ping Naume Bjørn Børresen-Dale Anne-Lise Kristensen Vessela N Prokunina-Olsson Ludmila <it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations Molecular Cancer |
author_facet |
Ambs Stefan Fosså Sophie D Landmark-Høyvik Hege Shah Anushi Porter-Gill Patricia Kohaar Indu Howe Tiffany M Arhancet Juan P Kaushiva Alpana Edvardsen Hege Fu Yi-Ping Naume Bjørn Børresen-Dale Anne-Lise Kristensen Vessela N Prokunina-Olsson Ludmila |
author_sort |
Ambs Stefan |
title |
<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations |
title_short |
<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations |
title_full |
<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations |
title_fullStr |
<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations |
title_full_unstemmed |
<it>NOTCH2 </it>in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without <it>TP53 </it>mutations |
title_sort |
<it>notch2 </it>in breast cancer: association of snp rs11249433 with gene expression in er-positive breast tumors without <it>tp53 </it>mutations |
publisher |
BMC |
series |
Molecular Cancer |
issn |
1476-4598 |
publishDate |
2010-05-01 |
description |
<p>Abstract</p> <p>Background</p> <p>A recent genome-wide association study (GWAS) has identified a single nucleotide polymorphism (SNP) rs11249433 in the 1p11.2 region as a novel genetic risk factor for breast cancer, and this association was stronger in patients with estrogen receptor (ER)<sup>+ </sup>versus ER<sup>- </sup>cancer.</p> <p>Results</p> <p>We found association between SNP rs11249433 and expression of the <it>NOTCH2 </it>gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of <it>NOTCH2 </it>was found to be lowest in tumors with <it>TP53 </it>mutations and highest in <it>TP53 </it>wild-type/ER<sup>+ </sup>tumors (p = 0.0059). In the latter group, the <it>NOTCH2 </it>expression was particularly increased in carriers of the risk genotypes (AG/GG) of rs11249433 when compared to the non-risk AA genotype (p = 0.0062). Similar association between <it>NOTCH2 </it>expression and rs11249433 was observed in 60 samples of purified monocytes from healthy controls (p = 0.015), but not in total blood samples from 302 breast cancer patients and 76 normal breast tissue samples. We also identified the first possible dominant-negative form of <it>NOTCH2</it>, a truncated version of <it>NOTCH2 </it>consisting of only the extracellular domain.</p> <p>Conclusion</p> <p>This is the first study to show that the expression of <it>NOTCH2 </it>differs in subgroups of breast tumors and by genotypes of the breast cancer-associated SNP rs11249433. The NOTCH pathway has key functions in stem cell differentiation of ER<sup>+ </sup>luminal cells in the breast. Therefore, increased expression of <it>NOTCH2 </it>in carriers of rs11249433 may promote development of ER<sup>+ </sup>luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of <it>NOTCH2 </it>expression by rs11249433 and the role of <it>NOTCH2 </it>splicing forms in breast cancer development.</p> |
url |
http://www.molecular-cancer.com/content/9/1/113 |
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