Heritable Retinoblastoma: Genotype–Phenotype Correlations

Abstract

Abstract: : Purpose: To employ mutation analysis to predict disease expression in patients with heritable retinoblastoma (RB). Methods: Consecutive patients with heritable retinoblastoma who had undergone mutation analysis performed at Universitiy of California, San Francisco, or the Hospital for Sick Children, University of Toronto between 1980 and 2001 were identified. The medical records of these patients were retrospectively analysed and the severity of disease categorized based upon clinical variables including 1. age at onset of disease, 2. stage of disease at presentation, and 3. clinical disease course. Disease severity was then correlated with underlying RB mutations. Results: 123 patients with complete clinical information and who also had a RB mutation identified using either karyotype analysis, protein truncation testing, fluorescent in situ hybridization or quantitative multiplex–polymerase chain reaction, were evaluated. Conclusions: The patient's genotype may be correlated with observed clinical phenotype by grouping mutations according to the predicted degrees of RB protein dysfunction. In the future, this approach may allow patients to be stratified based upon a knowledge of the underlying genetic abnormality. This may have implications for prognosis and therapy. In situations where identical mutations are associated with various clinical outcomes, other genetic alterations may contribute to the outcome and are currently the focus of further investigation.

Keywords: retinoblastoma • genetics • oncology