Morison I M, Becroft D M, Taniguchi T, Woods C G, Reeve A E
Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Nat Med. 1996 Mar;2(3):311-6. doi: 10.1038/nm0396-311.
Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic features of BWS. Three children showed constitutional abnormalities of H19 methylation. All four children showed nephromegaly and two developed Wilms' tumors. Gene methylation is known to be associated with gene silencing, and three children showed constitutional abnormalities of H19 gene methylation. Disruption of H19 methylation, and concomitant relaxation of IGF2 imprinting, provides another mechanism that can increase IGF2 expression in children with overgrowth. The accumulated data on normal and pathologic IGF2 expression are now sufficient to define an entity, "IGF2 overgrowth disorder," of which BWS may be one extreme manifestation. These findings have broad implications for the characterization of idiopathic overgrowth.
通常呈印记状态的胎儿胰岛素样生长因子II（IGF2）的过表达与易患癌症的贝克威思-维德曼综合征（BWS）的发病机制有关。我们在四名身体过度生长但无BWS诊断特征的儿童中检测到IGF2印记的体质性松弛。三名儿童表现出H19甲基化的体质性异常。所有四名儿童均出现肾肿大，两名儿童患了肾母细胞瘤。已知基因甲基化与基因沉默有关，三名儿童表现出H19基因甲基化的体质性异常。H19甲基化的破坏以及随之而来的IGF2印记松弛，为过度生长儿童中IGF2表达增加提供了另一种机制。目前，关于正常和病理性IGF2表达的累积数据足以定义一个实体，即“IGF2过度生长障碍”，其中BWS可能是一种极端表现。这些发现对特发性过度生长的特征描述具有广泛意义。
