title: Genetic and epigenetic alterations of RB2/p130 tumor suppressor gene in human sporadic retinoblastoma: implications for pathogenesis and therapeutic approach.
abstract: Human retinoblastoma occurs in two forms (familial and sporadic) both due to biallelic mutation of the RB1/p105 gene even if its loss is insufficient for malignancy. We have recently reported that loss of expression of the retinoblastoma-related protein pRb2/p130 correlates with low apoptotic index, suggesting that RB2/p130 gene could be involved in retinoblastoma. Mutational analysis of RB2/p130 in primary tumors showed a tight correlation between Exon 1 mutations and pRb2/p130 expression level in sporadic retinoblastoma. These mutations are located within a CpG-enriched region prone to de novo methylation. Analysis of RB2/p130 methylation status revealed that epigenetic events, most probably consequent to the Exon 1 mutations, determined the observed phenotype. Treatment of Weri-Rb1 cell line by 5-Aza-dC induced an increase in expression level of pRb2/p130, E2F1, p73 and p53. Overall, our results highlight a crucial role of epigenetic events in sporadic retinoblastoma, which opens a perspective for new therapeutic approaches.
authors: Department of Ophthalmology and Neurosurgery, University of Siena, Italy.
authors: Gian Marco
authors: GM
authors: Tosi
authors: Carmela
authors: C
authors: Trimarchi
authors: Marcella
authors: M
authors: Macaluso
authors: Dario
authors: D
authors: La Sala
authors: Alfredo
authors: A
authors: Ciccodicola
authors: Stefano
authors: S
authors: Lazzi
authors: Mina
authors: M
authors: Massaro-Giordano
authors: Aldo
authors: A
authors: Caporossi
authors: Antonio
authors: A
authors: Giordano
authors: Caterina
authors: C
authors: Cinti
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004252:DNA Mutational Analysis; D017931:DNA Primers; D000077209:Decitabine; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D019572:Retinal Neoplasms / Q000235:genetics*; D012175:Retinoblastoma / Q000235:genetics*; D050717:Retinoblastoma-Like Protein p130
chemical_list: D017931:DNA Primers; D011506:Proteins; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130; D000077209:Decitabine; D001374:Azacitidine