Loss of imprinting of the IGF-II and H19 genes in epithelial ovarian cancer

To establish a possible role of genomic imprinting in the carcinogenesis of epithelial ovarian cancer, we determined the imprinting status of both IGF -lr and H19 genes in 43 ovarian cancers, 7 low malignant potential ovarian tumors, and their matched normal tissues. In ovarian cancer, loss of hetero zygosity (LOH) of IGF-II, H19 RsaI, and H19 AluI was found in 4 of 24 (16.7 %), 3 of 20 (15%), and 1 of 16 (6.3%) samples, respectively. All patients w ith tumor specimens exhibiting LOH are of advanced clinical stages. Loss of imprinting (LOI) was found in 5 of 20 (25%) for IGF-II and in 3 of 17 (23. 5%) and 1 of 15 (6.7%) for the RsaI and AluI sites of H19 gene with no LOH, However, no LOH Has found in low malignant potential tumors, and only one of them showed LOI in H19 AluI site. Overexpression of IGF-II was demonstra ted in all five LOI samples with normal expression of H19, Three of the fiv e tumor specimens exhibiting LOT were transcribed from P1 promoter, whereas the remaining two were from the P3 promoter. These results suggested that LOB of both IGF-II and H19 genes was associated with advanced ovarian cance r. LOI of IGF-II and H19 genes may be involved in the development of ovaria n cancer. Transcription of IGF-II from the PI promoter may account far the biallelic expression of the IGF-II gene.