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Japanese Journal of Clinical Oncology, Vol 28, Issue 6 383-387, Copyright © 1998 by Foundation for Promotion of Cancer Research

ORIGINAL ARTICLE

Point mutations of ornithine decarboxylase gene are an infrequent event in colorectal cancer but a missense mutation was found in a replication error positive patient with hMSH2 germline mutation

M Maekawa, K Sugano, H Kashiwabara, M Ushiama, S Fujita, H Ohkura and T Kakizoe
Division of Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan. mmaekawa@gan2.ncc.go.gp

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.
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