Abstract
We have examined the imprinting of the insulin–like growth factor II gene (IGF2) in ten normal kidney samples from children with renal embryonal neoplasms. In kidney samples from nine children with normal growth profiles, IGF2 mRNA was transcribed monoallelically, consistent with normal imprinting of the gene. But in one child who had generalized somatic overgrowth, IGF2 was transcribed from both alleles in her kidney, peripheral blood leukocytes and Wilms' tumour. These findings suggest that a defect in genomic imprinting can occur constitutionally, leading to growth abnormalities and predisposition to Wilms' tumour.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
DeChiara, M., Robertson, E.J. & Efstratiadis, A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64, 849–859 (1991).
Rainier, S. et al. Relaxation of imprinted genes in human cancer. Nature 362, 747–749 (1993).
Ogawa, O. et al. Relaxation of insulin-like growth factor gene imprinting implicated in Wilms' tumour. Nature 362, 749–751 (1993).
Ohlsson, R. et al. IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome. Nature Genet. 4, 94–97 (1993).
Giannoukakis, N., Deal, C., Paquette, J., Goodyer, C.G., Polychronakos, C. Parental genomic imprinting of the human IGF2 gene. Nature Genet. 4, 98–101 (1993).
Moore, T. & Haig, D. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7, 45–49 (1991).
Reik, W. Genomic imprinting and genetic disorders in man. Trends Genet. 5, 331–336 (1989).
Koufos, A.I. et al. Familial Wiedemann-Beckwith syndrome and a second Wilms' tumor locus both map to 11p15.5. Am. J. hum. Genet. 44, 711–719 (1989).
Ping, A.J. et al. Genetic linkage of Beckwith-Wiedemann syndrome to 11 p15 Am. J. hum. Genet. 44, 720–723 (1989).
Aleck, K.A. & Hadro, T.A. Dominant inheritance of Wiedemann-Beckwith syndrome: further evidence for transmission of ‘unstable premutation’ through carrier women. Am. J. med. Genet. 33, 155–160 (1989).
Moutou, C., Junien, C., Henry, I. & Bonaiti-Pellie, C. Beckwith-Wiedemann syndrome: a demonstration of the mechanisms responsible for the excess of transmitting females. J. med. Genet. 29, 217–220 (1992).
Viljoen, D. & Ramesar, R. Evidence for paternal imprinting in familial Beckwith-Wiedemann syndrome. J. med. Genet. 29, 221–225 (1992).
Maldonado, V., Gaynon, P.S. & PoznanskiA, K. Cerebralgigantism associated with Wilms' tumor Am. J. Dis. Child 138, 486–488 (1984).
Reeve, A.E., Eccles, M.R., Wilkins, R.J.W., Bell, G.I. & Millow, L.J. Expression of insulin-like growth factor-ll transcripts in Wilms' tumour. Nature 317, 258–260 (1985).
Scott, J. et al. Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues. Nature 317, 261–262 (1985).
Bunin, G.R., Kramer, S., Marrero, O. & Meadows, A.T. Gestational risk factors for Wilms' tumor: results of a case-control study. Cancer Res. 47, 2972–2977 (1987).
Little, M.H., Clarke, J., Byrne, J., Dunn, R. & Smith, P.J. Allelic loss on chromosome 11 p is a less frequent event in bilateral than in unilateral Wilms' tumours. Eur. J. Cancer 28A, 1879–1883 (1992).
Mannens, M. et al. Loss of heterozygosity in Wilms' tumors, studied for six putative tumor suppressor regions, is limited to chromosome 11. Cancer Res. 50, 3279–3283 (1990).
Chao, L-Y. et al. Genetic mosaicism in normal tissues of Wilms' tumour patients. Nature Genet. 3, 127–131 (1993).
Henry, I. et al. Somatic mosaicism for partial paternal isodisomy in Wiedemann-Beckwith syndrome: a post-fertilisation event. Eur. J. hum. Genet. 1, 19–29 (1993).
Henry, I. et al. Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 361, 665–667 (1991).
Grundy, P. et al. Chromosome 11 uniparental isodisomy predisposing to embryonal neoplasms. Lancet 338, 1079–1080 (1991).
Ferguson-Smith, A.C., Cattanach, B.M., Barton, S.C., Beechey, C.V. & Surani, M.A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature 361, 667–670 (1991).
Bartolomei, M.S. & Tilghman, S.M. Parental imprinting of the mouse H19 gene. Nature 361 153–155 (1991).
Tadokoro, K., Fujii, H., Inoue, T. & Yamada, M. Polymerase chain reaction (PCR) for detection of Apal polymorphism at the insulin like growth factor II gene (IGF2). Nucl. Acids Res. 19, 6961 (1991).
Dilworth, D.D. & McCarrey, J.R. Single-step elimination of contaminating DNA prior to reverse transcriptase PCR. PCR Meth. Applic. 1, 279–282 (1992).
Hamill, P.V.V. NHCS growth curves for children. US Department of Health Education and Welfare (PHS) 78–1650, 1–74 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogawa, O., Becroft, D., Morison, I. et al. Constitutional relaxation of insulin–like growth factor II gene imprinting associated with Wilms' tumour and gigantism. Nat Genet 5, 408–412 (1993). https://doi.org/10.1038/ng1293-408
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng1293-408
- Springer Nature America, Inc.
This article is cited by
-
Hallmark discoveries in the biology of Wilms tumour
Nature Reviews Urology (2024)
-
Regulation of IGF2 transcript and protein expression by altered methylation in breast cancer
Journal of Cancer Research and Clinical Oncology (2011)
-
Candidate genes and potential targets for therapeutics in Wilms’ tumour
Clinical and Translational Oncology (2010)
-
In silico regulatory analysis for exploring human disease progression
Biology Direct (2008)
-
Nephroblastom — Wilms-Tumor
Der Onkologe (2005)