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Loss of Imprinting of the Insulin-like Growth Factor II Gene in Renal Cell Carcinoma¹

Department of Urology, Osaka University Medical School, 2-2 Yamada-oka, Suita-city, Osaka 565 [N. N., K. N., T. M., N. K., Y. K., A. O.]; and Department of Urology, Ehime University, Shizukawa, Shigenobu-cho, Onsen-gun, Ehime 791-02, Japan [M. Y.]

Loss of imprinting (LOI) has been implicated in the pathogenesis of embryonal malignancies as well as adult cancers. Insulin-like growth factor II (IGF2) gene is an imprinted gene, normally transcribed only from the paternal allele. We investigated allele-specific expression of the IGF2 gene in 22 cases of renal cell carcinoma (RCC), a common adultonset renal tumor. Sixteen cases (72%) were informative for IGF2 gene expression, and 9 (56%) of these cases showed biallelic expression of the IGF2 gene. Additionally, in four cases with biallelic expression from which uninvolved kidney tissue was available, LOI of the IGF2 gene was also demonstrated in the normal tissue. All cases with LOI of IGF2 were low-grade and low-stage tumors. LOI of the IGF2 gene in RCC was not associated with overexpression of IGF2 mRNA, whereas IGF2 overexpression was frequently observed in high-stage tumors. These results suggest that LOI of IGF2 predisposes to low-grade and low-stage tumors, whereas IGF2 overexpression may have a role in RCC tumor progression.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture of Japan.

² These authors made equal contributions to this work.

³ To whom requests for reprints should be addressed. Phone: 81-6-879-3531; Fax: 81-6-879-3539; E-mail: nono@uro.med.osaka-u.ac.jp.

Received 2/24/97. Accepted 5/12/97.

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