The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum.
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.
Ouyang
H
H
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Shiwaku
H O
HO
Hagiwara
H
H
Miura
K
K
Abe
T
T
Kato
Y
Y
Ohtani
H
H
Shiiba
K
K
Souza
R F
RF
Meltzer
S J
SJ
Horii
A
A
D001943:Breast Neoplasms / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics; D005260:Female; D006657:Histones / Q000235:genetics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013274:Stomach Neoplasms / Q000235:genetics
D004273:DNA, Neoplasm; D006657:Histones; D017527:Receptor, IGF Type 2