miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs.
miRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs.
复制标题
DOI：
10.1186/bcr3415
复制
发表时间：
2013-04-19
期刊：
影响因子：
--
通讯作者：
Martens JW
中科院分区：
文献类型：
--
作者：
Riaz M;van Jaarsveld MT;Hollestelle A;Prager-van der Smissen WJ;Heine AA;Boersma AW;Liu J;Helmijr J;Ozturk B;Smid M;Wiemer EA;Foekens JA;Martens JW
乳腺癌是一种遗传和表型复杂的疾病。为了了解miRNA在这种分子复杂性中的作用，我们在一组分子特征良好的人类乳腺癌细胞系中进行了miRNA表达分析，以确定与最常见的分子亚型和最常见的遗传畸变相关的miRNA。使用携带LNA™修饰的寡核苷酸捕获探针的微阵列，在51个乳腺癌细胞系中测量了725种人类mirna的表达水平。通过无监督聚类分析探讨了差异miRNA表达，然后将其与乳腺癌中常见的分子亚型和遗传畸变联系起来。使用最可变表达的mirna进行无监督聚类分析，将51个乳腺癌细胞系分为大簇和小簇，主要反映乳腺癌细胞系的管腔和基底固有细分。113个mirna在这两个主要集群之间存在差异表达。40种mirna在基底样和正常样/低claudin细胞系之间存在差异表达。在luminal-组中，39个mirna与ERBB2过表达相关，24个mirna与E-cadherin基因突变相关，这在该亚型乳腺癌细胞系中很常见。相反，31个mirna与E-cadherin启动子超甲基化相关，这与E-cadherin突变相反，仅在非腔内起源的乳腺癌细胞系中观察到。有30种mirna与p16INK4状态相关，而只有少数mirna与BRCA1、PIK3CA/PTEN和TP53突变状态相关。12个mirna与相应位点的DNA拷贝数变异相关。基底和上皮间充质相关的miRNA决定了乳腺癌细胞系miRNA转录组的细分。特定的mirna组与ERBB2过表达、p16INK4a或E-cadherin突变或E-cadherin甲基化状态相关，这意味着这些mirna可能有助于这些遗传畸变的驱动作用。此外，mirna位于显示复发性遗传畸变的基因组区域，其本身可能在乳腺癌发生中起驱动作用，或有助于其附近的驱动基因。总之，我们的研究提供了乳腺癌细胞系详细的分子miRNA图谱，可用于临床重要miRNA的功能研究。
Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations. Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with ERBB2 overexpression and 24 with E-cadherin gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with p16INK4 status while only a few miRNAs were associated with BRCA1, PIK3CA/PTEN and TP53 mutation status. Twelve miRNAs were associated with DNA copy number variation of the respective locus. Luminal-basal and epithelial-mesenchymal associated miRNAs determine the subdivision of miRNA transcriptome of breast cancer cell lines. Specific sets of miRNAs were associated with ERBB2 overexpression, p16INK4a or E-cadherin mutation or E-cadherin methylation status, which implies that these miRNAs may contribute to the driver role of these genetic aberrations. Additionally, miRNAs, which are located in a genomic region showing recurrent genetic aberrations, may themselves play a driver role in breast carcinogenesis or contribute to a driver gene in their vicinity. In short, our study provides detailed molecular miRNA portraits of breast cancer cell lines, which can be exploited for functional studies of clinically important miRNAs.
登录
查看更多内容
影响因子：
11.2
作者：
Elyakim, Eran;Sitbon, Einat;Yerushalmi, Noga
通讯作者：
Yerushalmi, Noga
影响因子：
3.7
作者：
Enerly E;Steinfeld I;Kleivi K;Leivonen SK;Aure MR;Russnes HG;Rønneberg JA;Johnsen H;Navon R;Rødland E;Mäkelä R;Naume B;Perälä M;Kallioniemi O;Kristensen VN;Yakhini Z;Børresen-Dale AL
通讯作者：
Børresen-Dale AL
影响因子：
4.5
作者：
Christoffersen, Nanna Ronbjerg;Silahtaroglu, Asli;Lund, Anders H.
通讯作者：
Lund, Anders H.
影响因子：
11.2
作者：
Hurteau, Gregory J.;Carlson, J. Andrew;Brock, Graham J.
通讯作者：
Brock, Graham J.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM