Skip to main content

01-01-2015 | Ophthalmologic cancers | Article

2. Challenges of Genetic Susceptibility Testing for Retinoblastoma

Author: M.S., C.G.C. Megan Harlan Fleischut

Publisher: Springer International Publishing


Retinoblastoma (RB) has heritable and non-heritable forms. Testing patients with the heritable form of RB has identified different types of germline RB1 mutations in DNA from either all of the leukocytes in a patient’s blood sample or less often, in a subset of the leukocytes (which is called mosaicism). Unusual mechanisms such as inheritance from the paternal allele affecting disease penetrance or the involvement of other genes such as MED4 have been described. Testing patients with the non-heritable form has revealed mechanisms including promoter hypermethylation and loss of heterozygosity in RB1−/− retinoblastomas. The involvement of the MYCN oncogene has been suggested in a small subset of sporadic unilateral tumors in which the RB1 gene is not mutated. As more patients undergo RB1 genetic testing and laboratory methodologies continually improve, the realm of possible results will further expand. Patients with RB and their families should be introduced to the possible results and the potential uses, risks, and limitations prior to undergoing testing. Having contact with genetics professionals at the disclosure of results and in the future is also recommended. Genetic counselors are part of a multidisciplinary team caring for patients with RB. This chapter’s focus is on the role of genetics professionals and the challenges that clinicians face with the interpretation and complexities of germline testing for these patients.

Please log in to get access to this content

Related topics