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Loss of Imprinting in Hepatoblastoma¹

Departments of Medicine, Oncology, and Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

We and others have described loss of imprinting (LOI) of the insulin-like growth factor II (IGF2) gene in 70% of Wilms' tumors (WT), an embryonal kidney tumor, and we have also found LOI of the H19 gene in 29% of WTs. In WT, LOI of IGF2 is coupled to down-regulation of H19. LOI of IGF2 has subsequently been described in a second embryonal neoplasm, rhabdomyosarcoma. However, the hypothesis that LOI is a general feature of embryonal tumors is challenged by a report of absence of LOI in three hepatoblastomas (S. M. Davies, Cancer Res., 53: 4781–4783, 1993). We identified five hepatoblastomas informative for a transcribed polymorphism of the IGF2 gene. One tumor showed LOI of IGF2, in contrast to the previous report. That tumor also showed LOI of H19, further documenting a role for this gene in imprinting disturbances in cancer. However, in contrast to WT, LOI in hepatoblastoma was not associated with down-regulation of H19. Thus, IGF2 and H19 expression can be uncoupled in tumors with LOI.

¹ This study was supported by United States Public Health Service Grant CA65145 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at 1064 Ross, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205.

Received 2/ 6/95. Accepted 3/17/95.

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