High incidence of allelic loss at 16q12.2 region spanning RBL2/p130 gene in retinoblastoma.

Retinoblastoma (Rb) is the most common intra-ocular tumor that manifests in early childhood. It is initiated by the inactivation of RB1/p105 gene, a prototype tumor suppressor gene. However, observed recurrent chromosomal aberrations accompanying RB1/p105 mutations suggest the involvement of additional mutational events. Chromosome 16q is one of the loci with recurrent losses which are likely to contain tumor suppressor genes. In this study, allelic loss was demonstrated at a second locus for retinoblastoma, RBL2/p130 on 16q12.2. Using intragenic single nucleotide polymorphisms (SNPs) (rs1074182 and rs10748) and flanking extragenic microsatellite markers (D16S411 and D16S408), 40 retinoblastoma tumor samples were analyzed. Loss of heterozygosity (LOH) of these markers was found in 11 (57.9%) out of 19 informative tumors at the RBL2/p130 gene locus and while a total of 15 (78.9%) tumors showed LOH in at least one marker. Deletions extending more than 13 cM across the pericentromeric region of 16q12.1-q13 were inferred from four tumors. Microsatellite instability was observed in two other tumors at the flanking markers. No mutations were found in RBL2/p130 exons 19-22 coding for the protein domain critical for biological activity. This is the first evidence of LOH within RBL2/p130 gene in retinoblastoma. The high frequency of allelic loss provides further evidence on the implication of this gene in retinoblastoma development and/or progression.