Absence of oncogenic canonical pathway mutations in aggressive pediatric rhabdoid tumors

Pediatr Blood Cancer. 2012 Dec 15;59(7):1155-7. doi: 10.1002/pbc.24315. Epub 2012 Sep 19.


Background: Rhabdoid tumors (also called atypical teratoid/rhabdoid tumor (AT/RT) in the brain), are highly malignant, poor prognosis lesions arising in the kidneys, soft tissues, and central nervous system. Targeted therapy in this disease would benefit from advanced technologies detecting relevant actionable mutations.

Procedure: Here we report on the evaluation of 25 tumors, all with known SMARCB1/INI1 alterations, for the presence of 983 different mutations in 115 oncogenes and tumor-suppressor genes using OncoMap, a mass spectrometric method of allele detection.

Results: Other than mutations in SMARCB1, our results identified a single activating mutation in NRAS and complete absence of oncogenic mutations in all other genes tested.

Conclusion: The absence of mutations in canonical pathways critical for development and progression of adult cancers suggests that distinct mechanisms drive these highly malignant pediatric tumors. This may limit the therapeutic utility of available targeted therapies and require a refocusing toward developmental and epigenetic pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, Tumor Suppressor
  • Genotyping Techniques
  • Humans
  • Infant
  • Male
  • Mass Spectrometry
  • Mutation*
  • Oncogenes / genetics
  • Rhabdoid Tumor / genetics*
  • SMARCB1 Protein
  • Signal Transduction / genetics*
  • Transcription Factors / genetics*


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors