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Somatic overgrowth associated with overexpression of insulin–like growth factor II

Nature Medicine volume 2, pages 311–316 (1996)Cite this article

Abstract

Overexpression of the normally imprinted fetal insulin–like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer–predisposing Beckwith–Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic features of BWS. Three children showed constitutional abnormalities of H19 methylation. All four children showed nephromegaly and two developed Wilms' tumors. Gene methylation is known to be associated with gene silencing, and three children showed constitutional abnormalities of HI9 gene methylation. Disruption of H19 methylation, and concomitant relaxation of IGF2 imprinting, provides another mechanism that can increase IGF2 expression in children with overgrowth. The accumulated data on normal and pathologic IGF2 expression are now sufficient to define an entity, “IGF2 overgrowth disorder,” of which BWS may be one extreme manifestation. These findings have broad implications for the characterization of idiopathic overgrowth.

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Authors and Affiliations

  1. Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin, New Zealand

    Ian M. Morison, Takanobu Taniguchi & Anthony E. Reeve

  2. Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

    David M. Becroft

  3. Yorkshire Regional Genetics Service, St James University Hospital, Leeds, UK

    C. Geoffrey Woods

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  4. C. Geoffrey Woods
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  5. Anthony E. Reeve
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Morison, I., Becroft, D., Taniguchi, T. et al. Somatic overgrowth associated with overexpression of insulin–like growth factor II. Nat Med 2, 311–316 (1996). https://doi.org/10.1038/nm0396-311

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