Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre and Department of Oncology, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
Breast Cancer Res. 2009;11(6):R88. doi: 10.1186/bcr2458. Epub 2009 Dec 10.
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.
正常基因表达的变异被认为在个体间变异和疾病易感性中起着核心作用。顺式作用元件中的调控多态性导致等位基因的表达不均等。杂合子个体中的差异等位基因表达（DAE）可用于开发一种新方法来发现调节乳腺癌易感性的基因座。由于获得大量新鲜的乳腺组织来进行此类研究较为困难，因此必须确定合适的替代测试组织，以便用于未来的研究。
我们测量了 12 个候选基因（可能与乳腺癌易感性相关的 BRCA1、BRCA2、C1qA、CCND3、EMSY、GPX1、GPX4、MLH3、MTHFR、NBS1、TP53 和 TRXR2）在健康个体的乳腺组织（n=40）和新鲜血液（n=170）以及 EBV 转化的淋巴母细胞（n=19）中的差异等位基因表达。通过 Taqman 测定法确定差异等位基因表达比率。使用 t 检验和 Wilcoxon 秩和检验分别比较均值比和方差比的比率分布。
我们表明，在这 12 个候选基因中，差异等位基因表达很常见，并且在很大一部分基因中，乳腺与血液（新鲜和转化的淋巴母细胞）之间的表达存在差异。我们发现，在乳腺和新鲜血液中具有 DAE 的九个基因中有八个是可比的，在乳腺和转化的淋巴母细胞中具有 DAE 的 11 个基因中有十个是可比的。
我们的研究结果支持在未来的乳腺癌易感性研究中，将血液中的差异等位基因表达用作乳腺组织的替代物。
