Alteration of hSNF5/INI1/BAF47 detected in rhabdoid cell lines and primary rhabdomyosarcomas but not Wilms' tumors

Oncogene. 1999 Dec 9;18(52):7559-65. doi: 10.1038/sj.onc.1203168.

Abstract

The organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting the access of transcriptional binding domains. The SWI/SNF family of chromatin-remodeling complexes, which are conserved from yeast to humans, open the chromatin to facilitate the transcriptional machinery to access their targets. The gene encoding the BAF47/hSNF5 subunit of the complex has been found mutated in both rhabdoid cell lines and in primary rhabdoid tumors. Since the pediatric tumors rhabdomyosarcoma (RMS) and Wilms' tumor (WT) share a similar genetic link with rhabdoid tumors, it was hypothesized that they may also show alterations of the BAF47 gene. Using primary tumors, the BAF47 protein was detected in all WT but less than 75% of the RMS tested. In cell lines, the BAF47 protein was missing in all rhabdoid cell lines and one RMS cell line. Analysis of sample DNA displayed either a mutation or deletion of the BAF47 gene in all samples negative for the protein. Several other subunits of the human SWI/SNF complex, including BRG1 which is the subunit directly interacting with the Rb tumor suppressor gene, were detected in all tumor samples. Alteration of BAF47 may be a genetic marker associated with the poor prognosis seen in all rhabdoid tumors but only some RMS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Blotting, Southern
  • Blotting, Western
  • Chromosomal Proteins, Non-Histone*
  • DNA Helicases
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Kidney Neoplasms / genetics*
  • Mutation
  • Nuclear Proteins / metabolism
  • Polymerase Chain Reaction
  • Rhabdoid Tumor / genetics*
  • Rhabdomyosarcoma / genetics*
  • SMARCB1 Protein
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Wilms Tumor / genetics*

Substances

  • ACTL6A protein, human
  • Actins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases