Challenges of Genetic Susceptibility Testing for Retinoblastoma
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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.
KeywordsCancer Gene Genetic counseling Genetic testing Heritable Mosaicism Retinoblastoma RB1
I want to thank Erin Salo-Mullen, M.S., C.G.C. and Zsofia Stadler, M.D. for their input for the design of this chapter and Richard Benz, M.S., U.S., Peter Fleischut, M.D. and Margaret Sheehan, M.S., C.G.C. for their review of this manuscript.
Compliance with Ethical Requirements
Megan Harlan Fleischut declares that she has no conflict of interest. No animal or human studies were carried out by the author for this article.
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