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Functionally inactivating point mutation in the tumor‐suppressor IRF‐1 gene identified in human gastric cancer
Author(s) -
Nozawa Hiroaki,
Oda Eri,
Ueda Seiji,
Tamura Gen,
Maesawa Chihaya,
Muto Tetsuichiro,
Taniguchi Tadatsugu,
Tanaka Nobuyuki
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980812)77:4<522::aid-ijc8>3.0.co;2-w
Subject(s) - loss of heterozygosity , biology , locus (genetics) , tumor suppressor gene , cancer research , gene , point mutation , allele , suppressor , mutant , carcinogenesis , microbiology and biotechnology , genetics
Loss of heterozygosity (LOH) observed in human tumors strongly suggests the existence of (a) tumor‐suppressor gene(s) at the concerned locus. A series of studies has revealed that LOH on the long arm of chromosome 5 (5q) frequently occurs in differentiated gastric adenocarcinomas. Furthermore, it has been shown that the interferon regulatory factor‐1 (IRF‐1) locus on chromosome 5q31.1 is one of the common minimal regions of LOH in these cancers. IRF‐1 is a transcriptional activator that shows tumor‐suppressor activity in the mouse. In the present study, we examined the sequence of the IRF‐1 gene in 9 cases of histologically differentiated gastric adenocarcinomas, all of which exhibited LOH at the IRF‐1 locus. We identified a mis‐sense mutation in the residual allele in one case. This mutated form of IRF‐1 showed markedly reduced transcriptional activity. In addition, over‐expression of wild‐type IRF‐1 induced cell‐cycle arrest, whereas such activity was attenuated in the mutant IRF‐1. These results suggest that the loss of functional IRF‐1 is critical for the development of human gastric cancers. Int. J. Cancer 77:522–527, 1998. © 1998 Wiley‐Liss, Inc.