Grupenmacher Alex T, Halpern Abby L, Bonaldo Maria de Fátima, Huang Chiang-Ching, Hamm Christopher A, de Andrade Alexandre, Tomita Tadanori, Sredni Simone T
Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box # 28, Chicago, IL, 60611, USA.
Childs Nerv Syst. 2013 Nov;29(11):1977-83. doi: 10.1007/s00381-013-2268-4. Epub 2013 Sep 3.
Malignant rhabdoid tumors (MRT) can occur in a variety of anatomical sites. The most frequent locations are the brain, where they are named atypical teratoid/rhabdoid tumors (AT/RT), and the kidney, where they are named rhabdoid tumors of the kidney (RTK). MRTs at all sites are recognized as the same entity due to their similar morphology, aggressive behavior, and a common genetic abnormality, an inactivating mutation of the SMARCB1/INI-1/hSNF5/BAF47 gene. We aim to investigate potential molecular differences between AT/RT and RTK.
We analyzed the microRNA (miRNA) and gene expression (GE) profiles of 10 RTK, 13 AT/RT, and 2 human MRT cell lines (G401-RTK and MON-AT/RT). Illumina V2 MicroRNA Chips (Illumina, Inc., CA, USA) were used for miRNA analysis, and Illumina HT-12 whole genome expression arrays were used for GE analysis.
The distribution of p values from GE showed a significant difference between RTK and AT/RT, with 20 % of the genes having p values ≤0.05 and the principal component analysis of the GE data showed separation between RTK and AT/RT. However, the miRNA expression failed to identify the different tumor groups. Among the 122 genes significantly differentially expressed between AT/RT and RTK, we found both genes related to brain development (i.e., FABP7, 22-fold increase in AT/RT) and genes related to kidney development (i.e., TCF21, sixfold increase in RTK).
Based on our results, we hypothesized that although MRT are indeed the same tumor, independent of the site of origin, the GE differences reflect the influence of microenvironment over tumor development.
恶性横纹肌样瘤（MRT）可发生于多种解剖部位。最常见的部位是脑，在脑内被称为非典型畸胎样/横纹肌样瘤（AT/RT），以及肾，在肾内被称为肾横纹肌样瘤（RTK）。所有部位的MRT因其相似的形态、侵袭性行为以及共同的基因异常——SMARCB1/INI-1/hSNF5/BAF47基因的失活突变，而被视为同一实体。我们旨在研究AT/RT和RTK之间潜在的分子差异。
我们分析了10例RTK、13例AT/RT以及2个人类MRT细胞系（G401-RTK和MON-AT/RT）的微小RNA（miRNA）和基因表达（GE）谱。使用Illumina V2微小RNA芯片（Illumina公司，美国加利福尼亚州）进行miRNA分析，使用Illumina HT-12全基因组表达阵列进行GE分析。
GE的p值分布显示RTK和AT/RT之间存在显著差异，20%的基因p值≤0.05，GE数据的主成分分析显示RTK和AT/RT之间有分离。然而，miRNA表达未能区分不同的肿瘤组。在AT/RT和RTK之间显著差异表达的122个基因中，我们发现了与脑发育相关的基因（即FABP7，在AT/RT中增加22倍）和与肾发育相关的基因（即TCF21，在RTK中增加6倍）。
基于我们的结果，我们推测尽管MRT确实是同一肿瘤，与起源部位无关，但GE差异反映了微环境对肿瘤发生发展的影响。
