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. 1997;76(11):1405–1409. doi: 10.1038/bjc.1997.570

The RB1 gene mutation in a child with ectopic intracranial retinoblastoma.

Z Onadim 1, A J Woolford 1, J E Kingston 1, J L Hungerford 1
PMCID: PMC2228178  PMID: 9400934

Abstract

The RB1 gene mutation was investigated in a child with ectopic intracranial retinoblastoma using DNA obtained from both the pineal and retinal tumours of the patient. A nonsense mutation in exon 17 (codon 556) of the RB1 gene was found to be present homozygously in both the retinal and the pineal tumours. The same mutation was present heterozygously in the DNA from the constitutional cells of the patient, proving it to be of germline origin. The initial mutation was shown to have occurred in the paternally derived RB1 allele. The mutation is in an area of the gene that encodes the protein-binding region known as the 'pocket' region and has been detected in other cases of retinoblastoma.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amoaku W. M., Willshaw H. E., Parkes S. E., Shah K. J., Mann J. R. Trilateral retinoblastoma. A report of five patients. Cancer. 1996 Aug 15;78(4):858–863. doi: 10.1002/(SICI)1097-0142(19960815)78:4<858::AID-CNCR24>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  2. Andrews J. D., Mancini D. N., Singh S. M., Rodenhiser D. I. Site and sequence specific DNA methylation in the neurofibromatosis (NF1) gene includes C5839T: the site of the recurrent substitution mutation in exon 31. Hum Mol Genet. 1996 Apr;5(4):503–507. doi: 10.1093/hmg/5.4.503. [DOI] [PubMed] [Google Scholar]
  3. Bader J. L., Meadows A. T., Zimmerman L. E., Rorke L. B., Voute P. A., Champion L. A., Miller R. W. Bilateral retinoblastoma with ectopic intracranial retinoblastoma: trilateral retinoblastoma. Cancer Genet Cytogenet. 1982 Mar;5(3):203–213. doi: 10.1016/0165-4608(82)90026-7. [DOI] [PubMed] [Google Scholar]
  4. Bader J. L., Miller R. W., Meadows A. T., Zimmerman L. E., Champion L. A., Voûte P. A. Trilateral retinoblastoma. Lancet. 1980 Sep 13;2(8194):582–583. doi: 10.1016/s0140-6736(80)92009-7. [DOI] [PubMed] [Google Scholar]
  5. Biegel J. A., Burk C. D., Barr F. G., Emanuel B. S. Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. Cancer Res. 1992 Jun 15;52(12):3391–3395. [PubMed] [Google Scholar]
  6. Blanquet V., Turleau C., Gross-Morand M. S., Sénamaud-Beaufort C., Doz F., Besmond C. Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma. Hum Mol Genet. 1995 Mar;4(3):383–388. doi: 10.1093/hmg/4.3.383. [DOI] [PubMed] [Google Scholar]
  7. Bullitt E., Crain B. J. Retinoblastoma as a possible primary intracranial tumor. Neurosurgery. 1981 Dec;9(6):706–709. doi: 10.1227/00006123-198112000-00016. [DOI] [PubMed] [Google Scholar]
  8. Cooper D. N., Krawczak M. The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. Hum Genet. 1990 Jun;85(1):55–74. doi: 10.1007/BF00276326. [DOI] [PubMed] [Google Scholar]
  9. Cooper D. N., Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet. 1988 Feb;78(2):151–155. doi: 10.1007/BF00278187. [DOI] [PubMed] [Google Scholar]
  10. Cowell J. K., Bia B., Akoulitchev A. A novel mutation in the promotor region in a family with a mild form of retinoblastoma indicates the location of a new regulatory domain for the RB1 gene. Oncogene. 1996 Jan 18;12(2):431–436. [PubMed] [Google Scholar]
  11. Cowell J. K., Smith T., Bia B. Frequent constitutional C to T mutations in CGA-arginine codons in the RB1 gene produce premature stop codons in patients with bilateral (hereditary) retinoblastoma. Eur J Hum Genet. 1994;2(4):281–290. doi: 10.1159/000472372. [DOI] [PubMed] [Google Scholar]
  12. De Potter P., Shields C. L., Shields J. A. Clinical variations of trilateral retinoblastoma: a report of 13 cases. J Pediatr Ophthalmol Strabismus. 1994 Jan-Feb;31(1):26–31. doi: 10.3928/0191-3913-19940101-06. [DOI] [PubMed] [Google Scholar]
  13. Draper G. J., Sanders B. M., Brownbill P. A., Hawkins M. M. Patterns of risk of hereditary retinoblastoma and applications to genetic counselling. Br J Cancer. 1992 Jul;66(1):211–219. doi: 10.1038/bjc.1992.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dryja T. P., Mukai S., Petersen R., Rapaport J. M., Walton D., Yandell D. W. Parental origin of mutations of the retinoblastoma gene. Nature. 1989 Jun 15;339(6225):556–558. doi: 10.1038/339556a0. [DOI] [PubMed] [Google Scholar]
  15. Dryja T. P., Rapaport J., McGee T. L., Nork T. M., Schwartz T. L. Molecular etiology of low-penetrance retinoblastoma in two pedigrees. Am J Hum Genet. 1993 Jun;52(6):1122–1128. [PMC free article] [PubMed] [Google Scholar]
  16. Dunn J. M., Phillips R. A., Zhu X., Becker A., Gallie B. L. Mutations in the RB1 gene and their effects on transcription. Mol Cell Biol. 1989 Nov;9(11):4596–4604. doi: 10.1128/mcb.9.11.4596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Friend S. H., Bernards R., Rogelj S., Weinberg R. A., Rapaport J. M., Albert D. M., Dryja T. P. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature. 1986 Oct 16;323(6089):643–646. doi: 10.1038/323643a0. [DOI] [PubMed] [Google Scholar]
  18. Griffin C. A., Hawkins A. L., Packer R. J., Rorke L. B., Emanuel B. S. Chromosome abnormalities in pediatric brain tumors. Cancer Res. 1988 Jan 1;48(1):175–180. [PubMed] [Google Scholar]
  19. Hahn M., Fislage R., Pingoud A. Polymorphism of the pentanucleotide repeat d(AAAAT) within intron 1 of the human tumor suppressor gene p53 (17p13.1). Hum Genet. 1995 Apr;95(4):471–472. doi: 10.1007/BF00208983. [DOI] [PubMed] [Google Scholar]
  20. Hogg A., Bia B., Onadim Z., Cowell J. K. Molecular mechanisms of oncogenic mutations in tumors from patients with bilateral and unilateral retinoblastoma. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7351–7355. doi: 10.1073/pnas.90.15.7351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hogg A., Onadim Z., Baird P. N., Cowell J. K. Detection of heterozygous mutations in the RB1 gene in retinoblastoma patients using single-strand conformation polymorphism analysis and polymerase chain reaction sequencing. Oncogene. 1992 Jul;7(7):1445–1451. [PubMed] [Google Scholar]
  22. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  23. Jakobiec F. A., Tso M. O., Zimmerman L. E., Danis P. Retinoblastoma and intracranial malignancy. Cancer. 1977 May;39(5):2048–2058. doi: 10.1002/1097-0142(197705)39:5<2048::aid-cncr2820390522>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  24. Kato M. V., Ishizaki K., Shimizu T., Ejima Y., Tanooka H., Takayama J., Kaneko A., Toguchida J., Sasaki M. S. Parental origin of germ-line and somatic mutations in the retinoblastoma gene. Hum Genet. 1994 Jul;94(1):31–38. doi: 10.1007/BF02272838. [DOI] [PubMed] [Google Scholar]
  25. Kees U. R., Biegel J. A., Ford J., Ranford P. R., Peroni S. E., Hallam L. A., Parmiter A. H., Willoughby M. L., Spagnolo D. Enhanced MYCN expression and isochromosome 17q in pineoblastoma cell lines. Genes Chromosomes Cancer. 1994 Feb;9(2):129–135. doi: 10.1002/gcc.2870090209. [DOI] [PubMed] [Google Scholar]
  26. Kingston J. E., Plowman P. N., Hungerford J. L. Ectopic intracranial retinoblastoma in childhood. Br J Ophthalmol. 1985 Oct;69(10):742–748. doi: 10.1136/bjo.69.10.742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Liu Z., Song Y., Bia B., Cowell J. K. Germline mutations in the RB1 gene in patients with hereditary retinoblastoma. Genes Chromosomes Cancer. 1995 Dec;14(4):277–284. doi: 10.1002/gcc.2870140406. [DOI] [PubMed] [Google Scholar]
  28. Lohmann D. R., Brandt B., Höpping W., Passarge E., Horsthemke B. Distinct RB1 gene mutations with low penetrance in hereditary retinoblastoma. Hum Genet. 1994 Oct;94(4):349–354. doi: 10.1007/BF00201591. [DOI] [PubMed] [Google Scholar]
  29. Lohmann D. R., Brandt B., Höpping W., Passarge E., Horsthemke B. The spectrum of RB1 germ-line mutations in hereditary retinoblastoma. Am J Hum Genet. 1996 May;58(5):940–949. [PMC free article] [PubMed] [Google Scholar]
  30. Moll A. C., Imhof S. M., Bouter L. M., Kuik D. J., Den Otter W., Bezemer P. D., Koten J. W., Tan K. E. Second primary tumors in patients with hereditary retinoblastoma: a register-based follow-up study, 1945-1994. Int J Cancer. 1996 Aug 7;67(4):515–519. doi: 10.1002/(SICI)1097-0215(19960807)67:4<515::AID-IJC9>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
  31. Onadim Z., Hogg A., Baird P. N., Cowell J. K. Oncogenic point mutations in exon 20 of the RB1 gene in families showing incomplete penetrance and mild expression of the retinoblastoma phenotype. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6177–6181. doi: 10.1073/pnas.89.13.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Onadim Z., Hogg A., Cowell J. K. Mechanisms of oncogenesis in patients with familial retinoblastoma. Br J Cancer. 1993 Nov;68(5):958–964. doi: 10.1038/bjc.1993.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Onadim Z., Hungerford J., Cowell J. K. Follow-up of retinoblastoma patients having prenatal and perinatal predictions for mutant gene carrier status using intragenic polymorphic probes from the RB1 gene. Br J Cancer. 1992 May;65(5):711–716. doi: 10.1038/bjc.1992.150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rodenhiser D., Chakraborty P., Andrews J., Ainsworth P., Mancini D., Lopes E., Singh S. Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs. Oncogene. 1996 Jun 20;12(12):2623–2629. [PubMed] [Google Scholar]
  35. Sakai T., Ohtani N., McGee T. L., Robbins P. D., Dryja T. P. Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene. Nature. 1991 Sep 5;353(6339):83–86. doi: 10.1038/353083a0. [DOI] [PubMed] [Google Scholar]
  36. Sreekantaiah C., Jockin H., Brecher M. L., Sandberg A. A. Interstitial deletion of chromosome 11q in a pineoblastoma. Cancer Genet Cytogenet. 1989 May;39(1):125–131. doi: 10.1016/0165-4608(89)90238-0. [DOI] [PubMed] [Google Scholar]
  37. Toguchida J., McGee T. L., Paterson J. C., Eagle J. R., Tucker S., Yandell D. W., Dryja T. P. Complete genomic sequence of the human retinoblastoma susceptibility gene. Genomics. 1993 Sep;17(3):535–543. doi: 10.1006/geno.1993.1368. [DOI] [PubMed] [Google Scholar]
  38. Vogel F., Rathenberg R. Spontaneous mutation in man. Adv Hum Genet. 1975;5:223–318. doi: 10.1007/978-1-4615-9068-2_4. [DOI] [PubMed] [Google Scholar]
  39. Weir-Thompson E., Condie A., Leonard R. C., Prosser J. A familial RB1 mutation detected by the HOT technique is homozygous in a second primary neoplasm. Oncogene. 1991 Dec;6(12):2353–2356. [PubMed] [Google Scholar]
  40. Yandell D. W., Campbell T. A., Dayton S. H., Petersen R., Walton D., Little J. B., McConkie-Rosell A., Buckley E. G., Dryja T. P. Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling. N Engl J Med. 1989 Dec 21;321(25):1689–1695. doi: 10.1056/NEJM198912213212501. [DOI] [PubMed] [Google Scholar]
  41. Yandell D. W., Dryja T. P. Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. Am J Hum Genet. 1989 Oct;45(4):547–555. [PMC free article] [PubMed] [Google Scholar]
  42. Zhu X. P., Dunn J. M., Phillips R. A., Goddard A. D., Paton K. E., Becker A., Gallie B. L. Preferential germline mutation of the paternal allele in retinoblastoma. Nature. 1989 Jul 27;340(6231):312–313. doi: 10.1038/340312a0. [DOI] [PubMed] [Google Scholar]
  43. Zimmerman L. E., Burns R. P., Wankum G., Tully R., Esterly J. A. Trilateral retinoblastoma: ectopic intracranial retinoblastoma associated with bilateral retinoblastoma. J Pediatr Ophthalmol Strabismus. 1982 Nov-Dec;19(6):320–325. doi: 10.3928/0191-3913-19821101-10. [DOI] [PubMed] [Google Scholar]

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