Institute of Biomedical Technology/BioMediTech, University of Tampere and Fimlab Laboratories, Tampere, Finland.
PLoS One. 2013 Aug 5;8(8):e72040. doi: 10.1371/journal.pone.0072040. Print 2013.
Prostate cancer (PCa) is a heterogeneous trait for which several susceptibility loci have been implicated by genome-wide linkage and association studies. The genomic region 13q14 is frequently deleted in tumour tissues of both sporadic and familial PCa patients and is consequently recognised as a possible locus of tumour suppressor gene(s). Deletions of this region have been found in many other cancers. Recently, we showed that homozygous carriers for the T442C variant of the ARLTS1 gene (ADP-ribosylation factor-like tumour suppressor protein 1 or ARL11, located at 13q14) are associated with an increased risk for both unselected and familial PCa. Furthermore, the variant T442C was observed in greater frequency among malignant tissue samples, PCa cell lines and xenografts, supporting its role in PCa tumourigenesis. In this study, 84 PCa cases and 15 controls were analysed for ARLTS1 expression status in blood-derived RNA. A statistically significant (p = 0.0037) decrease of ARLTS1 expression in PCa cases was detected. Regulation of ARLTS1 expression was analysed with eQTL (expression quantitative trait loci) methods. Altogether fourteen significant cis-eQTLs affecting the ARLTS1 expression level were found. In addition, epistatic interactions of ARLTS1 genomic variants with genes involved in immune system processes were predicted with the MDR program. In conclusion, this study further supports the role of ARLTS1 as a tumour suppressor gene and reveals that the expression is regulated through variants localised in regulatory regions.
前列腺癌（PCa）是一种具有异质性的特征，全基因组连锁和关联研究已经发现了几个易感基因座。13q14 基因组区域在散发性和家族性 PCa 患者的肿瘤组织中经常缺失，因此被认为是肿瘤抑制基因（s）的可能位置。该区域的缺失已在许多其他癌症中发现。最近，我们表明，ARLTS1 基因（ADP-核糖基化因子样肿瘤抑制蛋白 1 或 ARL11，位于 13q14）的 T442C 变体的纯合载体与未选择的和家族性 PCa 的风险增加相关。此外，在恶性组织样本、PCa 细胞系和异种移植中观察到变体 T442C 的频率更高，支持其在 PCa 肿瘤发生中的作用。在这项研究中，分析了 84 例 PCa 病例和 15 例对照者的血液衍生 RNA 中 ARLTS1 表达状态。在 PCa 病例中检测到 ARLTS1 表达的统计学显著（p=0.0037）降低。使用 eQTL（表达定量性状基因座）方法分析了 ARLTS1 表达的调节。总共发现了 14 个影响 ARLTS1 表达水平的显著顺式-eQTL。此外，使用 MDR 程序预测了 ARLTS1 基因组变异与参与免疫系统过程的基因之间的上位性相互作用。总之，这项研究进一步支持了 ARLTS1 作为肿瘤抑制基因的作用，并揭示了表达通过定位于调控区域的变体进行调节。
