Tumor-specific exon 1 mutations could be the 'hit event' predisposing Rb2/p130 gene to epigenetic silencing in lung cancer

Oncogene. 2005 Sep 1;24(38):5821-6. doi: 10.1038/sj.onc.1208880.


Genetic alterations in Rb2/p130 gene have been reported in several tumors, but till now there are insufficient and conflicting data linking the loss of pRb2/p130 expression with the mutational status of this gene in lung cancer. We recently reported that loss or lowering of pRb2/p130 expression is mainly due to aberrant Rb2/p130 promoter methylation, in retinoblastoma tumors, and indicated that epigenetic silencing of Rb2/p130 can impair its function to negatively regulate cell cycle progression as well as apoptotic response. In order to clarify Rb2/p130 gene inactivation in lung cancer, we investigated whether epigenetic events could impair the expression of this gene in NSLC. Here, we show that specific Rb2-exon 1 homozygous mutations, occurring in an Rb2/p130, region, rich in CpG dinucleotides, could be the 'hit event' that predispose this gene to epigenetic changes, leading to Rb2/p130 gene silencing in lung cancer. Moreover, these homozygous mutations, found in different tumor histotypes, could represent tumor-specific markers.

Publication types

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

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • Lung Neoplasms / genetics*
  • Models, Biological*
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • Retinoblastoma-Like Protein p130
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • Proteins
  • RBL2 protein, human
  • Retinoblastoma-Like Protein p130