High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival
High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival
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DOI：
10.1093/neuonc/nor140
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发表时间：
2011-12-01
期刊：
影响因子：
15.9
通讯作者：
Foreman, Nicholas K.
中科院分区：
文献类型：
--
作者：
Birks, Diane K.;Donson, Andrew M.;Foreman, Nicholas K.
肿瘤的分子谱分析已被证明是鉴定髓母细胞瘤、胶质母细胞瘤和其他癌症的预后和诊断亚组的宝贵工具。然而，非典型畸胎瘤样/横纹肌样瘤（AT/RT）的分子景观在很大程度上仍未被探索。为了解决这个问题，我们使用微阵列测量 18 个 AT/RT 的基因表达谱，并进行无监督的层次聚类以确定分子相似的亚组。确定了四个主要亚组（集群）。这些与性别、肿瘤位置或单体 22 的存在不符。簇显示出独特的基因特征和富集生物过程的差异，包括簇 4 中与脉络丛谱系相关的一些基因的表达升高。此外，各簇的生存期存在显着差异，与簇 1 和 2（平均 28.1 个月）相比，簇 3 和 4 中的生存期最短（平均 4.7 个月）。分析表明，多个骨形态发生蛋白 (BMP) 通路基因在短存活簇中上调，其中 BMP4 显示最显着的上调（270 倍）。因此，BMP 途径基因的高表达与该数据集中的生存呈负相关。我们的研究表明 AT/RT 中存在分子亚组，这些相对罕见的肿瘤的分子谱分析可能具有诊断、预后和治疗价值。
Molecular profiling of tumors has proven to be a valuable tool for identification of prognostic and diagnostic subgroups in medulloblastomas, glioblastomas, and other cancers. However, the molecular landscape of atypical teratoid/rhabdoid tumors (AT/RTs) remains largely unexplored. To address this issue, we used microarrays to measure the gene expression profiles of 18 AT/RTs and performed unsupervised hierarchical clustering to determine molecularly similar subgroups. Four major subgroups (clusters) were identified. These did not conform to sex, tumor location, or presence of monosomy 22. Clusters showed distinct gene signatures and differences in enriched biological processes, including elevated expression of some genes associated with choroid plexus lineage in cluster 4. In addition, survival differed significantly by cluster, with shortest survival (mean, 4.7 months) in both clusters 3 and 4, compared with clusters 1 and 2 (mean, 28.1 months). Analysis showed that multiple bone morphogenetic protein (BMP) pathway genes were upregulated in the short survival clusters, with BMP4 showing the most significant upregulation (270-fold). Thus, high expression of BMP pathway genes was negatively associated with survival in this dataset. Our study indicates that molecular subgroups exist in AT/RTs and that molecular profiling of these comparatively rare tumors may be of diagnostic, prognostic, and therapeutic value.