title: Tumor-specific exon 1 mutations could be the 'hit event' predisposing Rb2/p130 gene to epigenetic silencing in lung cancer.
abstract: 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.
authors.affiliation: Institute of Clinical Physiology, CNR, Siena Unity, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cinti
authors.forename: Marcella
authors.initials: M
authors.lastname: Macaluso
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D050717:Retinoblastoma-Like Protein p130; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130