Ward A
University of Bath, School of Biology and Biochemistry, Developmental Biology Programme, UK.
Mol Hum Reprod. 1997 Feb;3(2):157-68. doi: 10.1093/molehr/3.2.157.
Patients with rare overgrowth disorders, such as Beck-Wiedemann syndrome and Simpson-Golabi-Behmel syndrome, are predisposed to embryonal tumours, including Wilms' tumour of the kidney. Therefore, these disorders offer a link between hyperplastic growth and cancer. Genetic lesions at chromosome 11p15 have been associated with Beck-Wiedemann syndrome and Wilms' tumour for several years and the presence of the gene encoding insulin-like growth factor-II (IGF-II) in this region has given rise to much speculation over the involvement of this factor in these growth defects. This speculation was heightened by genetic evidence for the involvement of genomic imprinting in Beck-Wiedemann syndrome and Wilms' tumour, combined with the discovery that the IGF-II gene is imprinted. Although there is a wealth of evidence linking the IGF signalling pathway with overgrowth and cancer, recent progress in the study of 11p15 and developments in our understanding of the mechanism of genomic imprinting indicate that additional imprinted genes located in this region also contribute to these growth disorders.
患有罕见过度生长疾病的患者，如贝克-维德曼综合征和辛普森-戈拉比-贝梅尔综合征，易患胚胎性肿瘤，包括肾母细胞瘤。因此，这些疾病在增生性生长和癌症之间建立了联系。11号染色体p15区域的基因损伤与贝克-维德曼综合征和肾母细胞瘤相关数年，该区域存在编码胰岛素样生长因子-II（IGF-II）的基因，引发了人们对该因子参与这些生长缺陷的诸多猜测。基因组印记参与贝克-维德曼综合征和肾母细胞瘤的遗传证据，再加上IGF-II基因是印记基因这一发现，使得这种猜测更为强烈。尽管有大量证据将IGF信号通路与过度生长和癌症联系起来，但11p15研究的最新进展以及我们对基因组印记机制理解的发展表明，位于该区域的其他印记基因也导致了这些生长障碍。
