Ogawa O, Eccles M R, Szeto J, McNoe L A, Yun K, Maw M A, Smith P J, Reeve A E
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Nature. 1993 Apr 22;362(6422):749-51. doi: 10.1038/362749a0.
Genomic imprinting has been implicated in the onset of several embryonal tumours but the mechanism is not well understood. Maternal chromosome 11p15 loss of heterozygosity and paternal chromosome 11 isodisomy suggest that imprinted genes are involved in the onset of Wilms' tumour and the Beckwith-Wiedemann syndrome. The insulin-like growth factor II (IGF2) gene located at 11p15.5 has been put forward as a candidate gene as it is maternally imprinted (paternally expressed) in the mouse, and is expressed at high levels in Wilms' tumours. We report here that the IGF2 gene is expressed from the paternal allele in human fetal tissue, but that in Wilms' tumour expression can occur biallelically. These results provide, to our knowledge, the first evidence that relaxation of imprinting may play a role in the onset of disease and suggest a new genetic mechanism involved in the development of cancer.
基因组印记与几种胚胎肿瘤的发生有关，但其机制尚不清楚。母源11号染色体p15杂合性缺失和父源11号染色体等二体表明印记基因参与了肾母细胞瘤和贝克威思-维德曼综合征的发生。位于11p15.5的胰岛素样生长因子II（IGF2）基因已被提出作为候选基因，因为它在小鼠中是母源印记（父源表达）的，并且在肾母细胞瘤中高表达。我们在此报告，IGF2基因在人类胎儿组织中从父源等位基因表达，但在肾母细胞瘤中可双等位基因表达。据我们所知，这些结果首次证明印记放松可能在疾病发生中起作用，并提示了一种参与癌症发展的新遗传机制。
