Background: Retinoblastoma (RB) is a childhood ocular malignancy associated with mutations in RB1, a tumor susceptibility gene. Inactivation of both copies of the RB1 gene in a retinal cell is followed by the sequential acquisition of additional genetic changes that define the course to tumor formation.
Methods: To identify the genetic events that cooperate with loss of the RB1 gene function, we performed a whole genome sampling assay based on single nucleotide polymorphism genotyping. We used DNA isolated from 25 sporadic, unilateral RB tumors and matched blood samples.
Results: Genomic profiles were analyzed to identify regions of loss of heterozygosity or amplification. Two major subclasses of RB tumors were defined by the presence (n = 18) or absence (n = 7) of loss of heterozygosity of chromosome 13. Loss of heterozygosity in most cases was the result of copy-neutral events caused by mitotic recombination and mitotic nondisjunction. Tumors harbored novel regions of amplification at 1q44, 3p25, 11q14, 11q25, 14q23, 15q21, 16p13, 17p11.2, 19q13, and 20q13, whereas regions of loss included 6q22, 7q21, and 21q2.
Conclusion: Whole genome sampling assay-based analysis of unilateral RB tumors revealed novel regions as significant. These minimum critical regions that are lost or amplified are expected to harbor genes that aid the process of tumorigenesis.