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

Birks, Diane K., Donson, Andrew M., Patel, Purvi R., Dunham, Christopher, Muscat, Andrea, Algar, Elizabeth M., Ashley, David M., Kleinschmidt-Demasters, B. K., Vibhakar, Rajeev, Handler, Michael H. and Foreman, Nicholas K. 2011, High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival, Neuro-oncology, vol. 13, no. 12, pp. 1296-1307, doi: 10.1093/neuonc/nor140.

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Title High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival
Author(s) Birks, Diane K.
Donson, Andrew M.
Patel, Purvi R.
Dunham, Christopher
Muscat, Andrea
Algar, Elizabeth M.
Ashley, David M.
Kleinschmidt-Demasters, B. K.
Vibhakar, Rajeev
Handler, Michael H.
Foreman, Nicholas K.
Journal name Neuro-oncology
Volume number 13
Issue number 12
Start page 1296
End page 1307
Total pages 12
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2011-12
ISSN 1522-8517
1523-5866
Keyword(s) Biomarkers, Tumor
Bone Morphogenetic Proteins
Child, Preschool
Female
Gene Expression Profiling
Humans
Infant
Infant, Newborn
Male
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Rhabdoid Tumor
Teratoma
Science & Technology
Life Sciences & Biomedicine
Oncology
Clinical Neurology
Neurosciences & Neurology
Atypical teratoid/rhabdoid tumor
BMP4
bone morphogenetic protein pathway
microarray
survival
Summary 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.
Language eng
DOI 10.1093/neuonc/nor140
Field of Research 111207 Molecular Targets
1109 Neurosciences
1112 Oncology And Carcinogenesis
Socio Economic Objective 0 Not Applicable
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2011, The Author(s)
Persistent URL http://hdl.handle.net/10536/DRO/DU:30068986

Document type: Journal Article
Collection: School of Medicine
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