Retinoblastoma: Advances in Genetic Testing

Retinoblastoma is a genetic condition initiated by pathogenic variants causing biallelic loss of function of the RB1 gene. Genetic testing is a crucial component in the evaluation, treatment, and surveillance of retinoblastoma patients. A pathogenic germline mutation determines retinoblastoma heritability, a distinction that possesses significant implications for personal prognosis, risk assessments for family members, family planning, and clinical decision making. Any patient with a diagnosis of retinoblastoma with an uncertain RB1 status and first-degree relatives of probands with heritable disease should undergo genetic testing. The preferred method of testing for all probands is to first test tumor tissue if available. DNA from leukocytes from peripheral blood can then be analyzed for the specific variants identified in the tumor tissue to assess germline status. If no tumor tissue is available, peripheral blood is tested. If a germline variant is identified, at-risk family members can be tested for the specific variant with targeted sequencing. Newer testing technologies such as long-read sequencing hold significant promise due to its scalability globally and multi-omic capabilities, which provide new prognostic information. Improved access to testing in limited resource settings could improve patient outcomes.