High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival

Diane K. Birks, Andrew M Donson, Purvi R. Patel, Christopher Dunham, Andrea Muscat, Elizabeth M. Algar, David M. Ashley, B. K. Kleinschmidt-DeMasters, Rajeev Vibhakar, Michael H. Handler, Nicholas Olas K Foreman

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39 Citations (Scopus)

Abstract

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 lusters, 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 f these comparatively rare tumors may be of diagnostic, prognostic, and therapeutic value.

Original languageEnglish
Pages (from-to)1296-1307
Number of pages12
JournalNeuro-Oncology
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2011
Externally publishedYes

Keywords

  • Atypical teratoid/rhabdoid tumor
  • BMP4
  • Bone morphogenetic protein pathway
  • Microarray
  • Survival.

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