Ouyang H, Shiwaku H O, Hagiwara H, Miura K, Abe T, Kato Y, Ohtani H, Shiiba K, Souza R F, Meltzer S J, Horii A
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Cancer Res. 1997 May 15;57(10):1851-4.
Disruption of the DNA mismatch repair system, characterized by microsatellite instability (MI), plays an important role in the course of human carcinogenesis. Repetitive sequences constitute targets for mutation in MI+ cells, and frequent mutations have indeed been reported in such regions within the transforming growth factor beta receptor II (RII) gene in genetically unstable colorectal and gastric cancers. However, other genes that are targets for mutations in MI+ cells during the course of carcinogenesis have proven elusive. Because the insulin-like growth factor II receptor (IGFIIR) gene contains several repetitive sequences within its coding region, we examined mutations of this gene in MI+ cancers occurring at various primary sites. We found frameshift mutations in the poly(G)8 tract of IGFIIR in eight tumors, all of which were MI+: 4 of 26 (15%) MI+ endometrial cancers, 3 of 12 (25%) MI+ gastric cancers, and 1 of 18 (6%) MI+ colorectal cancers. In contrast, no mutation was found in 51 pancreatic cancers, 7 of which (14%) were MI+. These results implicate abnormal IGFIIR-mediated growth control in carcinogenesis involving the endometrium, stomach, and colorectum but not the pancreas.
以微卫星不稳定性（MI）为特征的DNA错配修复系统的破坏在人类致癌过程中起重要作用。重复序列是MI+细胞中突变的靶点，在基因不稳定的结直肠癌和胃癌中，转化生长因子β受体II（RII）基因内的此类区域确实已报道有频繁突变。然而，在致癌过程中作为MI+细胞中突变靶点的其他基因仍难以捉摸。由于胰岛素样生长因子II受体（IGFIIR）基因在其编码区内含有几个重复序列，我们检测了在各种原发部位发生的MI+癌症中该基因的突变情况。我们在8个肿瘤中发现了IGFIIR的poly(G)8区域的移码突变，所有这些肿瘤均为MI+：26例MI+子宫内膜癌中有4例（15%），12例MI+胃癌中有3例（25%），18例MI+结直肠癌中有1例（6%）。相比之下，在51例胰腺癌中未发现突变，其中7例（14%）为MI+。这些结果表明，在涉及子宫内膜、胃和结肠但不涉及胰腺的致癌过程中，IGFIIR介导的生长控制异常。
