title: Absence of oncogenic canonical pathway mutations in aggressive pediatric rhabdoid tumors.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Director, Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Pediatric Hematology/Oncology, Boston, MA 02215, USA. mark_kieran@dfci.harvard.edu
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kieran
authors.forename: Charles W M
authors.initials: CW
authors.lastname: Roberts
authors.forename: Susan N
authors.initials: SN
authors.lastname: Chi
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Rich
authors.forename: Laura E
authors.initials: LE
authors.lastname: Macconaill
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
mesh_terms: D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors