Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.
Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.
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DOI：
10.1186/bcr2458
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Ponder BA
中科院分区：
文献类型：
--
作者：
Maia AT;Spiteri I;Lee AJ;O'Reilly M;Jones L;Caldas C;Ponder BA
正常的基因表达变异被认为在个体间变异和疾病易感性中起着核心作用。顺式作用元件的调控多态导致等位基因的不平等表达。杂合子个体的差异等位基因表达(DAE)可能成为发现乳腺癌易感基因的新途径。由于很难获得大量新鲜的乳房组织来进行此类研究，因此必须为未来的研究确定合适的替代测试组织。我们检测了可能与乳腺癌易感性相关的12个候选基因(BRCA1、BRCA2、C1qA、CCND3、EMSY、GPX1、Gpx4、MLH3、MTHFR、NBS1、TP53和TRXR2)在健康个体和EBV转化的淋巴母细胞(n=19)的乳腺组织和新鲜血液中的差异等位基因表达。用Taqman法测定差异等位基因的表达比例。分别用t检验和Wilcoxon秩和检验比较均值比和方差比分布。我们发现，在这12个候选基因中，差异等位基因的表达是常见的，并且在乳房和血液(新鲜的和转化的淋巴母细胞)中有相当大的比例具有可比性。我们发现，在乳房和新鲜血液中，9个DAE基因中有8个是相似的，乳房和转化的淋巴母细胞之间的11个基因中有10个是相似的。我们的发现支持在未来关于乳腺癌易感性的研究中使用血液中不同的等位基因表达作为乳房组织的替代。
Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies. We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively. We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts. Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.
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影响因子：
12.3
作者：
Attanasio C;Reymond A;Humbert R;Lyle R;Kuehn MS;Neph S;Sabo PJ;Goldy J;Weaver M;Haydock A;Lee K;Dorschner M;Dermitzakis ET;Antonarakis SE;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
4.5
作者：
Choy E;Yelensky R;Bonakdar S;Plenge RM;Saxena R;De Jager PL;Shaw SY;Wolfish CS;Slavik JM;Cotsapas C;Rivas M;Dermitzakis ET;Cahir-McFarland E;Kieff E;Hafler D;Daly MJ;Altshuler D
通讯作者：
Altshuler D
影响因子：
3.2
作者：
Racila, E;Racila, DM;Weiner, GJ
通讯作者：
Weiner, GJ
影响因子：
7
作者：
Bjornsson, Hans T.;Albert, Thomas J.;Feinberg, Andrew P.
通讯作者：
Feinberg, Andrew P.
影响因子：
30.8
作者：
Spielman, Richard S.;Bastone, Laurel A.;Cheung, Vivian G.
通讯作者：
Cheung, Vivian G.