NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations.
NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumors without TP53 mutations.
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乳腺癌中的 NOTCH2：SNP rs11249433 与无 TP53 突变的 ER 阳性乳腺肿瘤中基因表达的关联。
DOI：
10.1186/1476-4598-9-113
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发表时间：
2010-05-19
期刊：
影响因子：
37.3
通讯作者：
Prokunina-Olsson, Ludmila
中科院分区：
文献类型：
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作者：
Fu, Yi-Ping;Edvardsen, Hege;Kaushiva, Alpana;Arhancet, Juan P.;Howe, Tiffany M.;Kohaar, Indu;Porter-Gill, Patricia;Shah, Anushi;Landmark-Hoyvik, Hege;Fossa, Sophie D.;Ambs, Stefan;Naume, Bjorn;Borresen-Dale, Anne-Lise;Kristensen, Vessela N.;Prokunina-Olsson, Ludmila
最近的一项全基因组关联研究（GWAS）发现1p11.2区域的单核苷酸多态性（SNP） rs11249433是乳腺癌的一个新的遗传危险因素，并且这种相关性在雌激素受体(ER)+与ER-癌症患者中更强。我们发现SNP rs11249433与位于1p11.2区域的NOTCH2基因表达之间存在关联。在180例乳腺肿瘤中，NOTCH2在TP53突变的肿瘤中表达最低，在TP53野生型/ER+肿瘤中表达最高（p = 0.0059）。在rs11249433的风险基因型（AG/GG）携带者中，NOTCH2的表达比非风险AA基因型携带者明显增加（p = 0.0062）。在来自健康对照的60个纯化单核细胞样本中观察到NOTCH2表达与rs11249433之间的类似关联（p = 0.015），但在302名乳腺癌患者和76名正常乳腺组织样本的总血液样本中没有观察到NOTCH2表达与rs11249433之间的类似关联。我们还发现了NOTCH2的第一种可能的显性阴性形式，这是NOTCH2的截断版本，仅由细胞外结构域组成。这是首次研究表明NOTCH2的表达在乳腺肿瘤亚组和乳腺癌相关SNP rs11249433的基因型中存在差异。NOTCH通路在乳腺ER+腔细胞的干细胞分化中起关键作用。因此，NOTCH2在rs11249433携带者中的表达增加可能促进ER+腔内肿瘤的发展。需要进一步研究rs11249433调控NOTCH2表达的可能机制以及NOTCH2剪接形式在乳腺癌发展中的作用。
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)+ versus ER- cancer. We found association between SNP rs11249433 and expression of the NOTCH2 gene located in the 1p11.2 region. Examined in 180 breast tumors, the expression of NOTCH2 was found to be lowest in tumors with TP53 mutations and highest in TP53 wild-type/ER+ tumors (p = 0.0059). In the latter group, the NOTCH2 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 NOTCH2 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 NOTCH2, a truncated version of NOTCH2 consisting of only the extracellular domain. This is the first study to show that the expression of NOTCH2 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+ luminal cells in the breast. Therefore, increased expression of NOTCH2 in carriers of rs11249433 may promote development of ER+ luminal tumors. Further studies are needed to investigate possible mechanisms of regulation of NOTCH2 expression by rs11249433 and the role of NOTCH2 splicing forms in breast cancer development.
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影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
4.2
作者：
Hirose, Hajime;Ishii, Hideshi;Mori, Masaki
通讯作者：
Mori, Masaki
影响因子：
39.2
作者：
LI, FP;FRAUMENI, JF
通讯作者：
FRAUMENI, JF
DOI：
10.1186/bcr1675
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Langerød A;Zhao H;Borgan Ø;Nesland JM;Bukholm IR;Ikdahl T;Kåresen R;Børresen-Dale AL;Jeffrey SS
通讯作者：
Jeffrey SS
影响因子：
4.5
作者：
Jia L;Landan G;Pomerantz M;Jaschek R;Herman P;Reich D;Yan C;Khalid O;Kantoff P;Oh W;Manak JR;Berman BP;Henderson BE;Frenkel B;Haiman CA;Freedman M;Tanay A;Coetzee GA
通讯作者：
Coetzee GA