Wada I, Kanada H, Nomura K, Kato Y, Machinami R, Kitagawa T
Department of Pathology, The Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, Japan.
Hepatology. 1999 Jun;29(6):1718-21. doi: 10.1002/hep.510290635.
The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) suppresses cell growth through binding to the insulin-like growth factor 2 (IGF2) and latent complex of the transforming growth factor-beta (TGF-beta). Recently, it was reported in the United States that loss of heterozygosity (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are frequent in hepatocellular carcinomas (HCCs) and adenomas. In view of the possible importance of this finding, especially for differential diagnosis of small hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasias (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patients in Japan for LOH using the polymorphic locus and for mutations by both single strand conformation polymorphism (SSCP) and direct sequencing methods. In the LOH study, 21 out of 22 informative HCCs and all of the informative AHs and RNs showed no allelic loss. In mutational studies of exons 27, 28, and 31, no mutations were detected either by SSCP or direct sequencing analysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene because of genetic alteration does not appear to be essential for hepatocarcinogenesis in Japan.
甘露糖-6-磷酸/胰岛素样生长因子2受体（M6P/IGF2R）通过与胰岛素样生长因子2（IGF2）及转化生长因子-β（TGF-β）的潜在复合物结合来抑制细胞生长。最近，美国有报道称，M6P/IGF2R基因第27、28和31外显子的杂合性缺失（LOH）及突变在肝细胞癌（HCC）和腺瘤中很常见。鉴于这一发现可能具有的重要性，特别是对于小肝病变的鉴别诊断，我们采用多态性位点分析LOH，并通过单链构象多态性（SSCP）和直接测序方法分析42例日本患者的43例原发性HCC、2例腺瘤样增生（AH）和3个再生结节（RN）中的突变情况。在LOH研究中，22例信息充分的HCC中有21例以及所有信息充分的AH和RN均未显示等位基因缺失。在第27、28和31外显子的突变研究中，48个病变中的任何一个通过SSCP或直接测序分析均未检测到突变。因此，在日本，因基因改变导致的M6P/IGF2R基因失活似乎并非肝癌发生所必需。
