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

Publication ,  Journal Article
Birks, DK; Donson, AM; Patel, PR; Dunham, C; Muscat, A; Algar, EM; Ashley, DM; Kleinschmidt-Demasters, BK; Vibhakar, R; Handler, MH; Foreman, NK
Published in: Neuro Oncol
December 2011

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.

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Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

December 2011

Volume

13

Issue

12

Start / End Page

1296 / 1307

Location

England

Related Subject Headings

  • Teratoma
  • Rhabdoid Tumor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Infant, Newborn
  • Infant
 

Citation

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Birks, D. K., Donson, A. M., Patel, P. R., Dunham, C., Muscat, A., Algar, E. M., … Foreman, N. K. (2011). High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival. Neuro Oncol, 13(12), 1296–1307. https://doi.org/10.1093/neuonc/nor140
Birks, Diane K., Andrew M. Donson, Purvi R. Patel, Christopher Dunham, Andrea Muscat, Elizabeth M. Algar, David M. Ashley, et al. “High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival.Neuro Oncol 13, no. 12 (December 2011): 1296–1307. https://doi.org/10.1093/neuonc/nor140.
Birks DK, Donson AM, Patel PR, Dunham C, Muscat A, Algar EM, et al. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival. Neuro Oncol. 2011 Dec;13(12):1296–307.
Birks, Diane K., et al. “High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival.Neuro Oncol, vol. 13, no. 12, Dec. 2011, pp. 1296–307. Pubmed, doi:10.1093/neuonc/nor140.
Birks DK, Donson AM, Patel PR, Dunham C, Muscat A, Algar EM, Ashley DM, Kleinschmidt-Demasters BK, Vibhakar R, Handler MH, Foreman NK. High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival. Neuro Oncol. 2011 Dec;13(12):1296–1307.
Journal cover image

Published In

Neuro Oncol

DOI

EISSN

1523-5866

Publication Date

December 2011

Volume

13

Issue

12

Start / End Page

1296 / 1307

Location

England

Related Subject Headings

  • Teratoma
  • Rhabdoid Tumor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction
  • RNA, Messenger
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Male
  • Infant, Newborn
  • Infant