No evidence for hypermethylation of the hSNF5/INI1 promoter in pediatric rhabdoid tumors

Genes Chromosomes Cancer. 2002 Aug;34(4):398-405. doi: 10.1002/gcc.10078.


The hSNF5/INI1 gene on chromosome 22 has been implicated as a tumor suppressor gene in pediatric rhabdoid tumor, an aggressive malignancy that generally occurs in the first two years of life. The most common sites for tumor development are the brain and kidney. We and other investigators have identified deletions and mutations of the INI1 gene in the majority of rhabdoid tumors of the central nervous system, kidney, and extrarenal tissues. At least 20% of cases do not have genomic alterations of INI1, although expression at the RNA or protein level may be decreased. The aim of this study was to determine whether hypermethylation or mutation of the 5' promoter region of INI1, or hypermethylation of CpG dinucleotides in a GC-rich repeat region within the first intron, could account for the decreased expression of INI1 observed in these tumors. We employed bisulfite modification, polymerase chain reaction, and sequence analysis to determine the methylation status of the cytosine nucleotides in the predicted promoter region of the INI1 gene, and two GC repeat regions in intron 1. DNA from 24 tumors with or without coding-sequence mutations was analyzed. None of the tumors demonstrated methylation of the promoter or intron 1 regions. This mechanism is unlikely to account for the inactivation of INI1 in rhabdoid tumors without coding-sequence mutations. One tumor demonstrated a potential mutation in the promoter region, but further studies are required for determining its functional significance.

Publication types

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

MeSH terms

  • 5' Untranslated Regions / genetics
  • Adolescent
  • Base Sequence
  • Child
  • Child, Preschool
  • Chromosomal Proteins, Non-Histone
  • DNA Methylation*
  • DNA Mutational Analysis / methods
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Dinucleotide Repeats / genetics
  • GC Rich Sequence / genetics
  • Humans
  • Infant
  • Introns / genetics
  • Molecular Sequence Data
  • Pediatrics
  • Promoter Regions, Genetic / genetics*
  • Rhabdoid Tumor / genetics*
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / pathology
  • SMARCB1 Protein
  • Sequence Analysis, DNA / methods
  • Transcription Factors
  • Tumor Cells, Cultured


  • 5' Untranslated Regions
  • Chromosomal Proteins, Non-Histone
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors