The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation

Nat Commun. 2016 Jan 28:7:10421. doi: 10.1038/ncomms10421.

Abstract

Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / chemically induced
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Male
  • Mice
  • Rhabdoid Tumor / chemically induced
  • Rhabdoid Tumor / genetics*
  • Rhabdoid Tumor / metabolism
  • SMARCB1 Protein
  • Tamoxifen / toxicity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Smarcb1 protein, mouse
  • Transcription Factors
  • Tamoxifen