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Activation of an imprinted allele of the insulin-like growth factor II gene implicated in rhabdomyosarcoma.
S Zhan, … , D N Shapiro, L J Helman
S Zhan, … , D N Shapiro, L J Helman
Published July 1, 1994
Citation Information: J Clin Invest. 1994;94(1):445-448. https://doi.org/10.1172/JCI117344.
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Activation of an imprinted allele of the insulin-like growth factor II gene implicated in rhabdomyosarcoma.

Abstract

The insulin-like growth factor II (IGF2) gene is exclusively silent at the maternal allele in the mouse as well as in normal human tissues and is expressed at a high level in rhabdomyosarcoma (RMS). We report here that the normally imprinted allele of the IGF2 gene is activated in RMS tumors as well as in one RMS cell line. Since overexpression of IGF2 has been shown to be important in the pathogenesis of RMS, our data suggest that loss of imprinting (LOI) may lead to overexpression of IGF2 and play an important role in the onset of RMS. Furthermore, embryonal RMS usually has loss of heterozygosity (LOH) with paternal disomy of the IGF2 locus. One informative embryonal RMS tumor evaluated in this study was heterozygous at the IGF2 allele and had LOI, raising the possibility that LOI may be the functional equivalent of LOH in this tumor with both events leading to overexpression of IGF2.

Authors

S Zhan, D N Shapiro, L J Helman

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