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Examination of IGF2 and H19 Loss of Imprinting in Bladder Cancer

¹ Division of Hematology and ² Department of Biochemistry, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California; and ³ Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland

Requests for reprints: Allen S. Yang, USC/Norris Cancer Center, 1441 Eastlake Ave., Room 6428, University of Southern California, CA 90033. Phone: 323-865-0712; E-mail: allenyan{at}usc.edu.

Loss of imprinting (LOI) is a common epigenetic event in cancer and may serve as an early biomarker in some cancers. To obtain a better understanding of LOI, we studied 41 bladder tumors and their adjacent normal bladder mucosa. We found 2/9 (22.2%) cases that displayed LOI of IGF2 and 2/16 (12.5%) that had LOI of H19, as determined by the evaluation of mRNA for biallelic expression. In addition, we examined allele-specific methylation of the differentially methylated regions (DMR) of IGF2 and H19 using a new allele-specific pyrosequencing assay. We found that DNA methylation changes were a common finding (21/30, 70%) in the DMR regions, but could not clearly link DNA methylation changes with LOI as measured by biallelic expression. LOI and allele-specific DNA methylation changes are present in bladder cancer; however, a better understanding of the biology of LOI and its relationship to DNA methylation changes is needed before its use as an epigenetic biomarker. [Cancer Res 2007;67(22):10753–8]