Takeda S, Kondo M, Kumada T, Koshikawa T, Ueda R, Nishio M, Osada H, Suzuki H, Nagatake M, Washimi O, Takagi K, Takahashi T, Nakao A, Takahashi T
Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, Nagoya, Japan.
Oncogene. 1996 Apr 4;12(7):1589-92.
It has been well documented that the liver is an exceptional organ in which the monoallelic expression of insulin-like growth factor 2 (IGF2) due to genomic imprinting is relaxed during the postnatal period, resulting in biallelic expression thereafter. In the present study, changes in the status of genomic imprinting were examined in 15 hepatocellular carcinomas (HCCs) as well as in 29 liver biopsies of chronic hepatitis or liver cirrhosis without clinical evidence of HCC, following screening for heterozygotes with an ApaI polymorphism in IGF2 in 34 HCCs and 80 such non-HCC cases. Extreme allelic-expression imbalance, leading to restoration of monoallelic IGF2 expression, was observed in 15 (100%) of 15 informative HCCs for the polymorphism with this monoallelic IGF2 expression appearing to be non-random from the paternal allele. Interestingly, the same allelic-expression imbalance was also present in a significant fraction of noncancerous liver specimens of patients with underlying disease known to be associated with HCC development. In contrast, the status of genomic imprinting of H19, another gene closely mapped at 11p15 under opposite imprinting, was strictly maintained in seven (100%) of seven cases informative for an RsaI polymorphism of H19. Together with the previous reports on altered genomic imprinting of IGF2 and H19 in embryonal lesions such as Wilms tumors as well as in lung cancers, the results suggest that perturbations of imprinting status occur as locus and tumor-type specific events in the development of human cancers.
已有充分文献记载，肝脏是一个特殊器官，在出生后时期，由于基因组印记，胰岛素样生长因子2（IGF2）的单等位基因表达会放松，此后导致双等位基因表达。在本研究中，在34例肝细胞癌（HCC）和80例无HCC临床证据的慢性肝炎或肝硬化肝活检样本中筛选出具有IGF2中ApaI多态性的杂合子后，检测了15例HCC以及29例此类非HCC病例中基因组印记状态的变化。在15例具有信息性的HCC中，有15例（100%）观察到极端等位基因表达失衡，导致单等位基因IGF2表达恢复，这种单等位基因IGF2表达似乎非随机地来自父本等位基因。有趣的是，在已知与HCC发生相关的潜在疾病患者的相当一部分非癌性肝脏标本中也存在相同的等位基因表达失衡。相比之下，在7例具有信息性的H19 RsaI多态性病例中，有7例（100%）严格维持了另一个紧密定位在11p15且印记相反的基因H19的基因组印记状态。连同之前关于Wilms肿瘤以及肺癌等胚胎性病变中IGF2和H19基因组印记改变的报道，这些结果表明印记状态的扰动在人类癌症发生过程中作为基因座和肿瘤类型特异性事件出现。
