title: E2F-4 mutation in hereditary non-polyposis colorectal cancer.
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.
authors.affiliation: Dept. of Gastroenterological Surgery and Surgical Oncology, Okayama University Graduate School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Moriyama
authors.forename: H
authors.initials: H
authors.lastname: Sasamoto
authors.forename: T
authors.initials: T
authors.lastname: Kambara
authors.forename: N
authors.initials: N
authors.lastname: Matsubara
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Baba
authors.forename: S J
authors.initials: SJ
authors.lastname: Meltzer
authors.forename: H T
authors.initials: HT
authors.lastname: Lynch
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: N
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D020137:Base Pair Mismatch; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D050704:E2F4 Transcription Factor; D006801:Humans; D018895:Microsatellite Repeats; D000074081:MutS Homolog 3 Protein; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D051028:bcl-2-Associated X Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; C094443:G-T mismatch-binding protein; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II