Frequent Loss of Imprinting of the H19 and IGF-II Genes in Ovarian Tumors

Abstract

Several human imprinted genes have been identified and are implicated in genetic dis- eases and tumorigenesis. We studied alter- ations of two imprinted genes, the pater- nally imprinted H19 and maternally im- printed IGF2, in 15 ovarian tumors with various cell types. To know allele-specific expression of the two genes, we analyzed re- striction fragment length polymorphisms (RFLPs) at the 3*-untranslated region (UTR) in their cDNA, compared with those in the respective genomic DNA. As a result, bialle- lic H19 and IGF2 expression was observed in 8 (62%) of 13 informative (heterozygous) ovarian cancers and in 6 of 11 informative cases, respectively. H19 loss of imprinting (LOI) was most frequently observed in ma- lignant serous cystadenocarcinoma (in four of six cases), whereas IGF2 LOI was not com- mon in malignant epithelial cancers be- cause three of six such LOI events occurred in benign mucinous cystadenomas and non- cancerous endometriotic cyst. Our data sug- gest that the alteration of H19 and IGF2 im- printing plays differential roles in tumori- genesis and progression of ovarian tumors, depending on the tissue type as well as the developmental stage. Our data may argue against tumor suppressor activity of H19 in ovarian cancers. Am. J. Med. Genet. 80:391– 395, 1998. © 1998 Wiley-Liss, Inc. KEY WORDS: genomic imprinting; H19; IGF2; ovarian cancer; carci- nogenesis