The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum.
The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum.
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发表时间：
1997-05
期刊：
影响因子：
11.2
通讯作者：
O. Hong;H. Shiwaku;H. Hagiwara;K. Miura;T. Abe;Y. Kato;H. Ohtani;K. Shiiba;R. Souza;S. Meltzer;A. Horii
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作者：
O. Hong;H. Shiwaku;H. Hagiwara;K. Miura;T. Abe;Y. Kato;H. Ohtani;K. Shiiba;R. Souza;S. Meltzer;A. Horii
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癌变过程中起着重要作用。重复序列构成MI+细胞的突变靶点，在遗传不稳定的结直肠癌和胃癌中，转化生长因子β受体II （RII）基因的这些区域确实报道了频繁的突变。然而，在癌变过程中作为MI+细胞突变靶点的其他基因已被证明是难以捉摸的。由于胰岛素样生长因子II受体（IGFIIR）基因在其编码区包含几个重复序列，因此我们研究了发生在不同原发部位的MI+癌症中该基因的突变。我们在8例MI+肿瘤中发现IGFIIR多(G)8通道移码突变：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，51例胰腺癌未发现突变，其中7例（14%）为MI+。这些结果暗示异常的igfiir介导的生长控制涉及子宫内膜、胃和结直肠，但不涉及胰腺。
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.