Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N–myc amplification

A Correction to this article was published on 01 August 1993

Abstract

Neuroblastomas frequently have deletions of chromosome 1 p and amplification of the N–myc oncogene. We analysed 53 neuroblastomas for the N–myc copy number, loss of heterozygosity (LOH) of chromosome 1 p36 and the parental origin of the lost alleles. Allelic loss of 1p36 was found in 15 tumours. All N–myc amplified tumours belonged to this subset. In 13/15 tumours with LOH of 1 p36 the lost allele was of maternal origin. This non–random distribution implies that the two alleles of the putative neuroblastoma suppressor gene on chromosome 1p36 are functionally different, depending on their parental origin. This is the first evidence as far as we know for genomic imprinting on chromosome 1p.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Brodeur, G.M. et al. Neuroblastoma; effect of genetic factors on prognosis and treatment. Cancer 70 Supplement, 1685–1694 (1992).

    Article  CAS  PubMed  Google Scholar 

  2. Fong, C.T. et al. Loss of heterozygosity for chromosome 1 or 14 defines a subset of advanced neuroblastomas. Cancer Res. 52, 1780–1785 (1992).

    CAS  PubMed  Google Scholar 

  3. Weith, A. et al. Neuroblastoma consensus deletion maps to 1p36.1-2. Genes. Chromosom. Cancer 1, 159–166 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Devilee, P. et al. Frequent somatic imbalance of marker alleles for chromosome 1 in human primary breast carcinoma. Cancer Res. 51, 1020–1025 (1991).

    CAS  PubMed  Google Scholar 

  5. Leister, I. et al. Human colorectal cancer: high frequency of deletions at chromosome 1p35. Cancer Res. 50, 7232–7235 (1990).

    CAS  PubMed  Google Scholar 

  6. Dracopoli, N.C. et al. Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumour progression. Proc. natn. Acad. Sci. U.S.A. 88, 4614–4618 (1989).

    Article  Google Scholar 

  7. Moley, J.F. et al. Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with Multiple Endocrine Neoplasia type 2 syndromes. Cancer Res. 52, 770–774 (1992).

    CAS  PubMed  Google Scholar 

  8. Mannens, M.M.A.M. et al. Molecular nature of genetic changes resulting in loss of heterozygosity of chromosome 11 in Wilms' tumours. Hum. Genet. 81, 41–48 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Schroeder, W.T. et al. Non-random loss of maternal chromosome 11 alleles in Wilms' tumours. Am. J. hum. Genet. 40, 413–420 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Pal, N. et al. Preferential loss of maternal alleles in sporadic Wilms' tumour. Oncogene 5, 1665–1668 (1990).

    CAS  PubMed  Google Scholar 

  11. Scrable, H. et al. A model for embryonal rhabdomyosarcoma tumorigenesis that involves genomic imprinting. Proc. natn. Acad. Sci. U.S.A. 86, 7480–7484 (1989).

    Article  CAS  Google Scholar 

  12. Toguchida, J. et al. Preferential mutation of paternally derived RB gene as the initial event in sporadic osteosarcoma. Nature 338, 156–158 (1989).

    Article  CAS  PubMed  Google Scholar 

  13. Sapienza, C. Genome imprinting and carcinogenesis. Biochim. Biophys. Acta 1072, 51–61 (1991).

    CAS  PubMed  Google Scholar 

  14. Hall, G.H. Genomic imprinting: review and relevance to human diseases. Am. J. hum. Genet. 46, 857–873 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Reik, W. Genomic imprinting and genetic disorders in man. Trends Genet. 5, 331–336 (1989).

    Article  CAS  PubMed  Google Scholar 

  16. Dryja, T.P. et al. Parental origin of mutations of the retinoblastoma gene. Nature 339, 556–558 (1989).

    Article  CAS  PubMed  Google Scholar 

  17. Stephens, K. et al. Preferential mutation of the neurofibromatosis type 1 gene in paternally derived chromosomes. Hum. Genet. 88, 279–282 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Zhu, X. et al. Preferential germline mutation of the paternal allele in retinoblastoma. Nature 340, 312–313 (1989).

    Article  CAS  PubMed  Google Scholar 

  19. Leach, R.J. et al. Preferential retention of the paternal alleles in human retinoblastoma: evidence for genomic imprinting. Cell Growth Diff. 1, 401–406 (1990).

    CAS  PubMed  Google Scholar 

  20. Kushner, B.H., Gilbert, F. & Helson, L. Familial neuroblastoma;case reports, literature review, and etiologic considerations. Cancer 57, 1887–1893 (1986).

    Article  CAS  PubMed  Google Scholar 

  21. Knudson, A.G. & Strong, L.C. Mutation and cancer: Neuroblastoma and pheochromocytoma. Am. J. hum. Genet. 24, 514–532 (1972).

    PubMed  PubMed Central  Google Scholar 

  22. Clausen, N., Andersson, P. & Tommerup, N. Familial occurrence of neuroblastoma, von Recklinghausen's neurofibromatosis, Hirsprung's aganglionosis and Jaw-winking syndrome. Acta Paediatr. Scand. 78, 736–741 (1989).

    Article  CAS  PubMed  Google Scholar 

  23. Robertson, C.M., Tyrrell, J.C. & Pritchard, J. Familial neural crest tumours. Eur. J. Pediatr. 150, 789–792 (1991).

    Article  CAS  PubMed  Google Scholar 

  24. Surani, M.A., Reik, W. & Allen, N.D. Transgenes as molecular probes for genomic imprinting. Trends Genet. 4, 59–62 (1988).

    Article  CAS  PubMed  Google Scholar 

  25. Hoovers, J.M.N., Dietrich, A.J.J. & Mannens, M.M.A.M. Imprinting and the Beckwith-Wiedemann syndrome. Lancet 339, 1228 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Versteeg, R. et al. N-myc expression switched off and class I human leucocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. Molec. cell Biol. 10, 5416–5423 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ellmeier, W., Aguzzi, A., Kleiner, E., Kurzbauer, R. & Weith, A. Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development. Embo J. 11, 2563–2571 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Evans, A.E., d'Angio, G.J. & Randolph, J. A proposed staging system for children with neuroblastoma. Cancer 27, 374–378 (1971).

    Article  CAS  PubMed  Google Scholar 

  29. Müllenbach, R., Lagoda, P.J.L. & Welter, C. An efficient salt-chloroform extraction of DNA from blood and tissues. Trends Genet. 5, 391 (1989).

    PubMed  Google Scholar 

  30. Feinberg, A.P. & Vogelstein, B.A. A technique for radio labeling DNA restriction endonuclease fragments to high specific activity. Annal. Biochem. 137, 266–267 (1989).

    Google Scholar 

  31. Schwab, M., Alitalo, K. & Klempnauer, K.H. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305, 245–248 (1983).

    Article  CAS  PubMed  Google Scholar 

  32. Derom, C. et al. Zygosity determination in newborn twins using DNA variants. J. med. Genet. 22, 279–282 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lauthier, V., Mariat, D. & Vergnaud, G. CEB15 detects a VNTR locus (het:92%) on chromosome 1p. Hum. molec. Genet. 1, 63 (1992).

    PubMed  Google Scholar 

  34. Dracopoli, N.C. et al. The CEPH consortium linkage map of human chromosome 1. Genomics 9, 686–700 (1991).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caron, H., van Sluis, P., van Hoeve, M. et al. Allelic loss of chromosome 1p36 in neuroblastoma is of preferential maternal origin and correlates with N–myc amplification. Nat Genet 4, 187–190 (1993). https://doi.org/10.1038/ng0693-187

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0693-187

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing