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  • Title: E2F-4 mutation in hereditary non-polyposis colorectal cancer.
    Author: Moriyama H, Sasamoto H, Kambara T, Matsubara N, Ikeda M, Baba S, Meltzer SJ, Lynch HT, Shimizu K, Tanaka N.
    Journal: J Exp Clin Cancer Res; 2002 Jun; 21(2):185-9. PubMed ID: 12148576.
    Abstract:
    Defects in the DNA mismatch repair function are known to cause microsatellite instability (MSI) in hereditary non-polyposis colorectal cancer (HNPCC) as well as in a subset of sporadic colorectal cancer (CRC). We previously reported that the E2F-4 gene, which encodes an important transcription factor in cell cycle control, had frequent tumor-specific mutations at a coding region of trinucleotide microsatellite (CAG)n in a subset of human sporadic CRC with high-frequency MSI (MSI-H). In this study, we assessed mutations of E2F-4 in HNPCC as well as other target genes of defective DNA mismatch repair function. Eighteen colorectal cancer (CRC) patients from 13 kindreds meeting the Amsterdam criteria for HNPCC were analyzed and compared to sporadic CRC patients with MSI-H. We detected mutations of E2F-4 at the same repeat sequence in HNPCC. The frequency of the E2F-4 mutation in HNPCC was comparable with that in sporadic CRC with MSI-H. E2F-4 was considered to be one of the important target genes responsible for the carcinogenesis of HNPCC.
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