Kim H T, Choi B H, Niikawa N, Lee T S, Chang S I
Department of Anatomy, Keimyung University School of Medicine, Taegu, Korea.
Am J Med Genet. 1998 Dec 4;80(4):391-5. doi: 10.1002/(sici)1096-8628(19981204)80:4<391::aid-ajmg16>3.0.co;2-h.
Several human imprinted genes have been identified and are implicated in genetic diseases and tumorigenesis. We studied alterations of two imprinted genes, the paternally imprinted H19 and maternally imprinted IGF2, in 15 ovarian tumors with various cell types. To know allele-specific expression of the two genes, we analyzed restriction fragment length polymorphisms (RFLPs) at the 3'-untranslated region (UTR) in their cDNA, compared with those in the respective genomic DNA. As a result, biallelic 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 malignant serous cystadenocarcinoma (in four of six cases), whereas IGF2 LOI was not common in malignant epithelial cancers because three of six such LOI events occurred in benign mucinous cystadenomas and non-cancerous endometriotic cyst. Our data suggest that the alteration of H19 and IGF2 imprinting plays differential roles in tumorigenesis 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.
几种人类印记基因已被识别，且与遗传疾病和肿瘤发生有关。我们研究了15例不同细胞类型的卵巢肿瘤中两个印记基因的改变情况，这两个基因分别是父系印记的H19和母系印记的IGF2。为了解这两个基因的等位基因特异性表达，我们分析了其cDNA 3'-非翻译区（UTR）的限制性片段长度多态性（RFLP），并与各自基因组DNA中的情况进行比较。结果显示，在13例信息充分（杂合）的卵巢癌中有8例（62%）观察到H19和IGF2的双等位基因表达，在11例信息充分的病例中有6例观察到双等位基因表达。印记丢失（LOI）在恶性浆液性囊腺癌中最为常见（6例中有4例），而IGF2的LOI在恶性上皮性癌中并不常见，因为6例此类LOI事件中有3例发生在良性黏液性囊腺瘤和非癌性子宫内膜异位囊肿中。我们的数据表明，H19和IGF2印记的改变在卵巢肿瘤的发生和进展中发挥不同作用，这取决于组织类型以及发育阶段。我们的数据可能与H19在卵巢癌中的肿瘤抑制活性观点相悖。
