Atypical teratoid/rhabdoid tumors-current concepts, advances in biology, and potential future therapies

Neuro Oncol. 2016 Jun;18(6):764-78. doi: 10.1093/neuonc/nov264. Epub 2016 Jan 10.


Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant CNS tumor of children below 6 months of age. The majority of AT/RTs demonstrate genomic alterations in SMARCB1 (INI1, SNF5, BAF47) or, to a lesser extent, SMARCA4 (BRG1) of the SWItch/sucrose nonfermentable chromatin remodeling complex. Recent transcription and methylation profiling studies suggest the existence of molecular subgroups. Thus, at the root of these seemingly enigmatic tumors lies a network of factors related to epigenetic regulation, which is not yet completely understood. While conventional-type chemotherapy may have significant survival benefit for certain patients, it remains to be determined which patients will eventually prove resistant to chemotherapy and thus need novel therapeutic strategies. Elucidation of the molecular consequences of a disturbed epigenome has led to the identification of a series of transduction cascades, which may be targeted for therapy. Among these are the pathways of cyclin D1/cyclin-dependent kinases 4 and 6, Hedgehog/GLI1, Wnt/ß-catenin, enhancer of zeste homolog 2, and aurora kinase A, among others. Compounds specifically targeting these pathways or agents that alter the epigenetic state of the cell are currently being evaluated in preclinical settings and in experimental clinical trials for AT/RT.

Keywords: AT/RT; BAF47; INI1; SMARCB1; SNF5; SWI/SNF; epigenetics; rhabdoid tumor.

Publication types

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

MeSH terms

  • Aurora Kinase A / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosomal Proteins, Non-Histone / therapeutic use*
  • Cyclin-Dependent Kinases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Epigenesis, Genetic / drug effects
  • Humans
  • Rhabdoid Tumor / metabolism
  • Rhabdoid Tumor / therapy*


  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Aurora Kinase A
  • Cyclin-Dependent Kinases