Mutation of the DNA methyltransferase (DNMT) 1 gene in human colorectal cancers.
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| Abstract |
Alteration of DNA methylation is one of the most consistent epigenetic changes in human cancers. DNA methyltransferase (DNMT) 1 is a major enzyme that determines genomic methylation patterns. In order to understand the significance of mutations of the DNMT1 gene during human carcinogenesis, we performed polymerase chain reaction-single strand conformation polymorphism analysis using 46 oligonucleotide primer sets for all 40 coding exons and the 5'-flanking region (450 bp) of the DNMT1 gene in 29 colorectal cancers, 32 stomach cancers, 40 hepatocellular carcinomas (HCCs) and a corresponding sample of non-cancerous tissue from each case. Mutations in coding exons of the DNMT1 gene were detected in two (7%) of the colorectal cancers: they consisted of one-base deletion resulting in deletion of the whole catalytic domain and a point mutation resulting in a single amino acid substitution. No stomach cancers or HCCs showed mutations in the coding exons of the DNMT1 gene. No mutation in the 5'-flanking region of the DNMT1 gene was detected in any of the colorectal and stomach cancers or HCCs. These data suggest that mutational inactivation of the DNMT1 gene that potentially causes a genome-wide alteration of DNA methylation status may be a rare event during human carcinogenesis.
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| Authors | Yae Kanai, Saori Ushijima, Yukihiro Nakanishi, Michiie Sakamoto, Setsuo Hirohashi |
| Journal | Cancer letters (Cancer Lett) Vol. 192 Issue 1 Pg. 75-82 (Mar 20 2003) ISSN: 0304-3835 [Print] Ireland |
| PMID | 12637155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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