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

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the firstrate-limiting enzyme in the biosynthesis of polyamines. ODC protein has acharacteristic amino acid sequence, the PEST sequence, which is related tothe enzyme's rapid degradation. ODC cDNA prepared from human hepatomatissues has been reported to show nonsense or missense mutations. METHODS:We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNAexpressions by RT-PCR in 50 colorectal cancer tissues to investigate theinvolvement of ODC gene alterations in colorectal cancers. RESULTS:Increased expression of the ODC gene was observed in 36 cases (86%) out ofthe 42 examined by RT-PCR. In one case, a missense mutation was found inthe cancer tissue but not in normal mucosa. The missense mutation from Aspto Asn at codon 424, in the PEST region, possibly stabilizes the ODCprotein. In colorectal cancer, replication error and a germline mutation inhMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424is speculated to be a cause of stabilization and a passenger mutation owingto the mutator phenotype. Since only one of 50 colorectal cancers exhibiteda missense mutation of the ODC gene, mutations in ODC gene are not frequentin colorectal cancer. The increased expression of the ODC gene was noted in86% of colorectal cancer tissues by RT-PCR, however, it was not due topoint mutations in ODC coding exons.