Chen C L, Ip S M, Cheng D, Wong L C, Ngan H Y
Department of Obstetrics and Gynecology, University of Hong Kong, S.A.R. China.
Clin Cancer Res. 2000 Feb;6(2):474-9.
To establish a possible role of genomic imprinting in the carcinogenesis of epithelial ovarian cancer, we determined the imprinting status of both IGF-II and H19 genes in 43 ovarian cancers, 7 low malignant potential ovarian tumors, and their matched normal tissues. In ovarian cancer, loss of heterozygosity (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 with 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 4 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 was found in low malignant potential tumors, and only one of them showed LOI in H19 AluI site. Overexpression of IGF-II was demonstrated in all five LOI samples with normal expression of H19. Three of the five tumor specimens exhibiting LOI were transcribed from P1 promoter, whereas the remaining two were from the P3 promoter. These results suggested that LOH of both IGF-II and H19 genes was associated with advanced ovarian cancer. LOI of IGF-II and H19 genes may be involved in the development of ovarian cancer. Transcription of IGF-II from the P1 promoter may account for the biallelic expression of the IGF-II gene.
为了确定基因组印记在上皮性卵巢癌致癌过程中的可能作用，我们检测了43例卵巢癌、7例低恶性潜能卵巢肿瘤及其配对正常组织中IGF-II和H19基因的印记状态。在卵巢癌中，IGF-II、H19 RsaI和H19 AluI的杂合性缺失（LOH）分别在24例样本中的4例（16.7%）、20例样本中的3例（15%）和16例样本中的1例（6.3%）中被发现。所有肿瘤标本显示LOH的患者均处于临床晚期。在20例IGF-II样本中有5例（25%）发现印记缺失（LOI），在H19基因的RsaI和AluI位点，17例中有4例（23.5%）和15例中有1例（6.7%）发现LOI，且无LOH。然而，在低恶性潜能肿瘤中未发现LOH，其中只有1例在H19 AluI位点显示LOI。在所有5例H19表达正常的LOI样本中均证实了IGF-II的过表达。5例显示LOI的肿瘤标本中有3例从P1启动子转录，其余2例从P3启动子转录。这些结果表明，IGF-II和H19基因的LOH与晚期卵巢癌相关。IGF-II和H19基因的LOI可能参与卵巢癌的发生发展。IGF-II从P1启动子的转录可能解释了IGF-II基因的双等位基因表达。
