De Souza A T, Hankins G R, Washington M K, Orton T C, Jirtle R L
Department of Safety of Medicines, Zeneca Pharmaceuticals, Macclesfield, Cheshire, UK.
Nat Genet. 1995 Dec;11(4):447-9. doi: 10.1038/ng1295-447.
The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) functions in the intracellular trafficking of lysosomal enzymes, the activation of the potent growth inhibitor, transforming growth factor beta 2, and the degradation of IGF2 (ref. 1), a mitogen often overproduced in tumours. We have recently shown that 70% of human hepatocellular tumours have loss of heterozygosity (LOH) at the M6P/IGF2R locus which maps to chromosome 6q26-q27 (ref. 8). Using a coarse screen, we have now identified point mutations in the remaining allele of 25% of human hepatocellular carcinomas (HCCs) with LOH. These mutations give rise to truncated receptor protein and significant amino acid substitutions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis.
甘露糖6-磷酸/胰岛素样生长因子-II受体（M6P/IGF2R）在溶酶体酶的细胞内运输、强效生长抑制剂转化生长因子β2的激活以及IGF2（参考文献1）的降解中发挥作用，IGF2是一种在肿瘤中常过度产生的有丝分裂原。我们最近发现，70%的人类肝细胞肿瘤在位于6号染色体6q26-q27的M6P/IGF2R基因座存在杂合性缺失（LOH）（参考文献8）。通过粗略筛选，我们现已在25%存在LOH的人类肝细胞癌（HCC）的剩余等位基因中鉴定出点突变。这些突变导致受体蛋白截短并出现显著的氨基酸替换，为M6P/IGF2R基因在人类肝癌发生过程中作为肿瘤抑制基因发挥作用提供了证据。
