Recent advances in retinoblastoma genetic research

Retinoblastoma is a pediatric eye tumor that serves as a paradigm for understanding the genetic basis of cancer. This review will highlight recent advances in retinoblastoma genetic research and discuss how these new findings influence our knowledge of retinoblastoma tumorigenesis and management.

Current data demonstrate that retinomas, benign retinal tumors found in some retinoblastoma patients, exhibit bi-allelic mutations in RB1, the retinoblastoma gene, and lack of expression of the retinoblastoma protein. Interestingly, retinomas demonstrate a low level of genomic instability that becomes progressively more severe in retinoblastoma tumors. Additionally, a subset of retinomas share genomic alterations with retinoblastoma. Collectively, these data suggest that retinomas represent true premalignant lesions and not regressed retinoblastoma tumors, as previously thought. Translational advances in retinoblastoma genetic research include development of an allele-specific assay that now enables the identification of mutational mosaicism, thereby increasing the rate of RB1 mutation detection in bilaterally affected patients to as high as 95%.

These and related research efforts reveal novel data that enhance our understanding of the biology of retinoblastoma. These observations may facilitate new therapeutic approaches to further decrease the morbidity and mortality associated with retinoblastoma and other more common forms of cancer.