Abstract
Retinoblastoma (Rb) is a malignant tumor that originates from developing retina. Diagnosis is based on clinical signs and symptoms and is usually made in children under the age of five years. Mutations in both alleles of the RB1 gene are a prerequisite for this tumor to develop. In most patients with sporadic unilateral Rb, both RB1 gene mutations occur in somatic cells and are not passed over to offspring (nonhereditary Rb). Almost all patients with sporadic bilateral and virtually all patients with familial Rb are heterozygous for RB1 gene mutations that cause predisposition to Rb (hereditary Rb). In families, Rb predisposition is transmitted as an autosomal dominant trait (familial Rb). In addition to Rb, patients with hereditary disease also have an increased risk of tumors outside the eye (second cancer). This risk is enhanced in patients who have received external beam radiotherapy. Analysis of genotype-phenotype associations has shown that the mean number of tumor foci that develop in carriers of mutant RB1 alleles is variable depending on which functions of the normal allele are retained and to what extent. Moreover, phenotypic expression of hereditary retinoblastoma is subject to genetic modification. Identification of the genetic factors that underlie these effects will not only help to arrive at a more precise prognosis but may also point to mechanisms that can be used to reduce the risk of tumor devel
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References
Xu XL, Fang Y, Lee TC et al. Retinoblastoma has properties of a cone precursor tumor and depends upon cone-specific MDM2 signaling. Cell 2009; 137:1018–1031.
Broaddus E, Topham A, Singh AD. Incidence of retinoblastoma in the USA: 1975-2004. Br J Ophthalmol 2009; 93:21–23.
Suckling RD, Fitzgerald PH, Stewart J et al. The incidence and epidemiology of retinoblastoma in New Zealand: A 30-year survey. Br J Cancer 1982; 46:729–736.
Olisa EG, Chandra R, Jackson MA et al. Malignant tumors in American black and Nigerian children: a comparative study. J Natl Cancer Inst 1975; 55:281–284.
Buckley JD. The aetiology of cancer in the very young. Br J Cancer 1992; (Suppl 18):S8–12.
Gillison ML, Chen R, Goshu E et al. Human retinoblastoma is not caused by known pRb-inactivating human DNA tumor viruses. Int J Cancer 2007; 120:1482–1490.
Odashiro AN, Pereira PR, de Souza Filho JP et al. Retinoblastoma in an adult: case report and literature review. Can J Ophthalmol 2005; 40:188–191.
Dimaras H, Khetan V, Halliday W et al. Loss of RB1 induces nonproliferative retinoma; increasing genomic instability correlates with progression to retinoblastoma. Hum Mol Genet 2008; 17:1363–1372.
Gallie BL, Ellsworth RM, Abramson DH et al. Retinoma: spontaneous regression of retinoblastoma or benign manifestation of the mutation? Br J Cancer 1982; 45:513–521.
Acquaviva A, Ciccolallo L, Rondelli R et al. Mortality from second tumour among long-term survivors of retinoblastoma: a retrospective analysis of the Italian retinoblastoma registry. Oncogene 2006; 25:5350–5357.
Kleinerman RA, Tucker MA, Tarone RE et al. Risk of new cancers after radiotherapy in long-term survivors of retinoblastoma: an extended follow-up. J Clin Oncol 2005; 23:2272–2279.
Kleinerman RA, Tucker MA, Abramson DH et al. Risk of soft tissue sarcomas by individual subtype in survivors of hereditary retinoblastoma. J Natl Cancer Inst 2007; 99:24–31.
Li FP, Abramson DH, Tarone RE et al. Hereditary retinoblastoma, lipoma and second primary cancers. J Natl Cancer Inst 1997; 89:83–84.
Rieder H, Lohmann D, Poensgen B et al. Loss of heterozygosity of the retinoblastoma (RB1) gene in lipomas from a retinoblastoma patient. J Natl Cancer Inst 1998; 90:324–326.
Abramson DH, Melson MR, Dunkel IJ et al. Third (fourth and fifth) nonocular tumors in survivors of retinoblastoma. Ophthalmology 2001; 108:1868–1876.
Yu CL, Tucker MA, Abramson DH et al. Cause-specific mortality in long-term survivors of retinoblastoma. J Natl Cancer Inst 2009; 101:581–591.
Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk. Ophthalmology 1998; 105:573–9; discussion 579-80.
Chauveinc L, Mosseri V, Quintana E et al. Osteosarcoma following retinoblastoma: age at onset and latency period. Ophthalmic Genet 2001; 22:77–88.
Gombos DS, Hungerford J, Abramson DH et al. Secondary acute myelogenous leukemia in patients with retinoblastoma: is chemotherapy a factor? Ophthalmology 2007; 114:1378–1383.
Lohmann DR, Gallie BL. Retinoblastoma: revisiting the model prototype of inherited cancer. Am J Med Genet C Semin Med Genet 2004; 129:23–28.
Kaelin A. Statistische Prüf-und Schätzverfahren für die relative Häufigkeit von Merkmalsträgern in Geschwisterreihen bei einem der Auslese unterworfenen Material mit Anwendung auf das Retinoblastom. Archiv der Julius Klaus-Stiftung 1955; 30:442–485.
Vogel F. (New studies on the genetics of retinoblastoma; glioma retinae.). Z Mensch Vererb Konstitutionsl 1957; 34:205–236.
Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68:820–823.
Godbout R, Dryja TP, Squire J et al. Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma. Nature 1983; 304:451–453.
Cavenee WK, Dryja TP, Phillips RA et al. Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 1983; 305:779–784.
Friend SH, Bernards R, Rogelj S et al. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323:643–646.
Genovese C, Trani D, Caputi M et al. Cell cycle control and beyond: emerging roles for the retinoblastoma gene family. Oncogene 2006; 25:5201–5209.
Stengel KR, Thangavel C, Solomon DA et al. RB/p107/130 pocket proteins: Protein dynamics and interactions with target gene promoters. J Biol Chem 2009.
Goodrich DW. The retinoblastoma tumor-suppressor gene, the exception that proves the rule. Oncogene 2006; 25:5233–5243.
Corson TW, Gallie BL. One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma. Genes Chromosomes Cancer 2007; 46:617–634.
Sánchez-Sánchez F, RamÃrez-Castillejo C, Weekes DB et al. Attenuation of disease phenotype through alternative translation initiation in low-penetrance retinoblastoma. Hum Mutat 2007; 28:159–167.
Zhang K, Nowak I, Rushlow D et al. Patterns of missplicing caused by RB1 gene mutations in patients with retinoblastoma and association with phenotypic expression. Hum Mutat 2008; 29:475–484.
Dryja TP, Rapaport J, McGee TL et al. Molecular etiology of low-penetrance retinoblastoma in two pedigrees. Am J Hum Genet 1993; 52:1122–1128.
Bremner R, Du DC, Connolly-Wilson MJ et al. Deletion of RB exons 24 and 25 causes low-penetrance retinoblastoma. Am J Hum Genet 1997; 61:556–570.
Otterson GA, Modi S, Nguyen K et al. Temperature-sensitive RB mutations linked to incomplete penetrance of familial retinoblastoma in 12 families. Am J Hum Genet 1999; 65:1040–1046.
Otterson GA, Chen W, Coxon AB et al. Incomplete penetrance of familial retinoblastoma linked to germ-line mutations that result in partial loss of RB function. Proc Natl Acad Sci USA 1997; 94:12036–12040.
Scheffer H, Van Der Vlies P, Burton M et al. Two novel germline mutations of the retinoblastoma gene (RB1) that show incomplete penetrance, one splice site and one missense. J Med Genet 2000; 37:E6.
Genuardi M, Klutz M, Devriendt K et al. Multiple lipomas linked to an RB1 gene mutation in a large pedigree with low penetrance retinoblastoma. Eur J Hum Genet 2001; 9:690–694.
Deschavanne PJ, Fertil B. A review of human cell radiosensitivity in vitro. Int J Radiat Oncol Biol Phys 1996; 34:251–266.
Chuang EY, Chen X, Tsai MH et al. Abnormal gene expression profiles in unaffected parents of patients with hereditary-type retinoblastoma. Cancer Res 2006; 66:3428–3433.
Wilson PF, Nagasawa H, Warner CL et al. Radiation sensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls: colony formation ability during continuous low-dose-rate gamma irradiation. Radiat Res 2008; 169:483–494.
Fitzek MM, Dahlberg WK, Nagasawa H et al. Unexpected sensitivity to radiation of fibroblasts from unaffected parents of children with hereditary retinoblastoma. Int J Cancer 2002; 99:764–768.
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Lohmann, D. (2010). Retinoblastoma. In: Ahmad, S.I. (eds) Diseases of DNA Repair. Advances in Experimental Medicine and Biology, vol 685. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6448-9_21
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DOI: https://doi.org/10.1007/978-1-4419-6448-9_21
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