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American Journal of Pathology, Vol 145, 802-817, Copyright © 1994 by American Society for Investigative Pathology

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The cell type-specific IGF2 expression during early human development correlates to the pattern of overgrowth and neoplasia in the Beckwith- Wiedemann syndrome

F Hedborg, L Holmgren, B Sandstedt and R Ohlsson
Department of Drug Dependence Research, Karolinska Hospital, Stockholm, Sweden.

Overstimulation by insulin-like growth factor II is implied in several overgrowth conditions and childhood cancers. We have therefore studied spatial and temporal expression patterns of the insulin-like growth factor II gene (IGF2) and the insulin-like growth factor type 1 receptor gene during normal human development (5.5 to 23.0 weeks postfertilization). The set of cell types with the most abundant IGF2 expression correlated strikingly to the organomegaly and tumor predisposition of the Beckwith-Wiedemann syndrome. Intrauterine growth and postnatal organ weights of a prematurely born child with a full- blown syndrome are presented. The cell type-specific IGF2 expression of these organs and of multifocal Wilms' tumors from two other children affected by the Beckwith-Wiedemann syndrome were also studied. The results clarify and extend previous findings concerning human prenatal IGF2 expression and are consistent with a short range overstimulatory role of locally produced IGF II ensuing after the first trimester in the Beckwith-Wiedemann syndrome.

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