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A Correction to this article was published on 24 September 2015


Retinoblastoma is a rare cancer of the infant retina that is diagnosed in approximately 8,000 children each year worldwide. It forms when both retinoblastoma gene (RB1) alleles are mutated in a susceptible retinal cell, probably a cone photoreceptor precursor. Loss of the tumour-suppressive functions of the retinoblastoma protein (pRB) leads to uncontrolled cell division and recurrent genomic changes during tumour progression. Although pRB is expressed in almost all tissues, cone precursors have biochemical and molecular features that may sensitize them to RB1 loss and enable tumorigenesis. Patient survival is >95% in high-income countries but <30% globally. However, outcomes are improving owing to increased disease awareness for earlier diagnosis, application of new guidelines and sharing of expertise. Intra-arterial and intravitreal chemotherapy have emerged as promising methods to salvage eyes that with conventional treatment might have been lost. Ongoing international collaborations will replace the multiple different classifications of eye involvement with standardized definitions to consistently assess the eligibility, efficacy and safety of treatment options. Life-long follow-up is warranted, as survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB1 loss in diverse tissues may open new avenues for treatment and prevention of retinoblastoma, as well as second cancers, in patients with germline RB1 mutations.

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Figure 1: Progression of retinoblastoma.
Figure 2: Global retinoblastoma treatment centres and patient distribution relative to resources.
Figure 3: Genetic origins of retinoblastoma.
Figure 4: Retinoblastomas originate in the retina.
Figure 5: Online diagnosis of retinoblastoma.
Figure 6: Different classification schemes for intraocular retinoblastoma confound comparison of outcomes.
Figure 7: Primary treatment choices based on the Murphree International Intraocular Retinoblastoma Classification.
Figure 8: Triplets with retinoblastoma.
Figure 9: Retinoblastoma treated with IVC.
Figure 10: Retinoblastoma treated with IAC.
Figure 11: Child Life programmes.
Figure 12: Proposed roles for cone precursor circuitry in retinoblastoma tumorigenesis and targeted therapy.


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T.W.C. acknowledges US NIH National Center for Advancing Translational Sciences grant KL2TR001106 and support from Research to Prevent Blindness, Inc. D.C. acknowledges NIH grant R01CA137124 and support from the Larry and Celia Moh Foundation and the Margaret E. Early Medical Research Trust. H.D. and B.L.G. acknowledge the TUYF Charitable Trust (Hong Kong).

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Introduction (B.L.G., H.D., D.C. and T.W.C.); Epidemiology (H.D., G.L.C., J.Z. and F.N.); Mechanisms/pathophysiology (T.W.C., D.C., H.D. and B.L.G.); Diagnosis, screening and prevention (H.D., G.L.C., J.Z. and B.L.G.); Management (F.L.M., C.L.S., D.H.A., G.L.C., F.N., J.Z. and B.L.G.); Quality of life (A.W., H.D. and B.L.G.); Outlook (all); overview of Primer (B.L.G. and H.D.).

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Correspondence to Brenda L. Gallie.

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Dimaras, H., Corson, T., Cobrinik, D. et al. Retinoblastoma. Nat Rev Dis Primers 1, 15021 (2015).

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