Wada M, Seeger R C, Mizoguchi H, Koeffler H P
Division of Hematology/Oncology, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine 90048, USA.
Cancer Res. 1995 Aug 1;55(15):3386-8.
H19 and insulin-like growth factor II (IGF2) are among a few genes which have been confirmed to be imprinted in normal human embryonal tissues. This results in monoallelic expression of maternal H19 and paternal IGF2. Loss of imprinting of these genes producing biallelic expression has been observed in Wilm's tumor and embryonal rhabdomyosarcoma, suggesting that an epigenetic change of DNA, in addition to a genetic change in oncogene(s) and/or tumor suppressor gene(s), may be involved in the development of these childhood cancers. Neuroblastoma, which is an embryonal tumor originating from neural crest-derived cells, occasionally occurs in individuals with the Beckwith-Wiedemann syndrome; Wilm's tumor and embryonal rhabdomyosarcoma occur even more frequently in the Beckwith-Wiedemann syndrome; and paternal uniparental disomy of H19 and IGF2 loci (chromosome 11p15) is present in the Beckwith-Wiedemann syndrome. Furthermore, neuroblastoma cell lines express IGF2, and autocrine/paracrine effects of IGF2 have been demonstrated in these cells. Thus, we examined for imprinting of both H19 and IGF2 in primary untreated neuroblastomas using the RsaI and ApaI polymorphisms within these genes, respectively. Seven of 15 tumors were informative for H19 and for IGF2, and all of these cases showed monoallelic expression of both of these genes. These results indicate that loss of imprinting of H19 and IGF2 does not occur in neuroblastomas.
H19和胰岛素样生长因子II（IGF2）是少数已被证实在正常人类胚胎组织中存在印记的基因。这导致母源H19和父源IGF2单等位基因表达。在威尔姆斯瘤和胚胎性横纹肌肉瘤中观察到这些基因印记丢失产生双等位基因表达，这表明除了癌基因和/或肿瘤抑制基因的遗传改变外，DNA的表观遗传变化可能也参与了这些儿童癌症的发生发展。神经母细胞瘤是一种起源于神经嵴衍生细胞的胚胎性肿瘤，偶尔发生于患有贝克威思-维德曼综合征的个体中；威尔姆斯瘤和胚胎性横纹肌肉瘤在贝克威思-维德曼综合征中更为常见；并且贝克威思-维德曼综合征患者存在H19和IGF2基因座（染色体11p15）的父源单亲二体性。此外，神经母细胞瘤细胞系表达IGF2，并且在这些细胞中已证实IGF2的自分泌/旁分泌作用。因此，我们分别利用这些基因内的RsaI和ApaI多态性，检测了未经治疗的原发性神经母细胞瘤中H19和IGF2的印记情况。15个肿瘤中有7个对H19和IGF2检测结果明确，所有这些病例均显示这两个基因的单等位基因表达。这些结果表明神经母细胞瘤中未发生H19和IGF2的印记丢失。
