title: Frameshift mutations at mononucleotide repeats in RAD50 recombinational DNA repair gene in colorectal cancers with microsatellite instability.
abstract: To identify additional genes targeted for microsatellite instability (MSI), we search for human genes which contain mononucleotide repeats in their coding region, selected 7 genes (RAD50, DNA-PKcs, FLASH, Apaf-1, XPG, CtIP, and MLSN1), and analyzed frameshift mutations in them. Here we report that 60% (3 out of 5) of human colorectal cancer cell lines exhibiting a high frequency of MSI (MSI-H) and 46% (6 out of 13) of MSI-H primary colorectal tumors had mutations in the (A)9 repeat of RAD50 recombinational repair gene. In contrast, no frameshift mutations were found in any of the 5 MSI-negative colorectal cancer cell lines, 8 colorectal tumors exhibiting a low frequency of MSI (MSI-L), or 28 MSI-negative colorectal tumors. No mutations were found in the mononucleotide repeats of 6 other genes, even in MSI-H cancers. These results suggest that RAD50 frameshift mutations may play a role in the tumorigenesis of MSI-H colorectal cancers.
authors: Department of Gastroenterology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. ikenoue-2im@h.u-tokyo.ac.jp
authors: T
authors: T
authors: Ikenoue
authors: G
authors: G
authors: Togo
authors: K
authors: K
authors: Nagai
authors: H
authors: H
authors: Ijichi
authors: J
authors: J
authors: Kato
authors: Y
authors: Y
authors: Yamaji
authors: M
authors: M
authors: Okamoto
authors: N
authors: N
authors: Kato
authors: T
authors: T
authors: Kawabe
authors: A
authors: A
authors: Tanaka
authors: M
authors: M
authors: Matsumura
authors: Y
authors: Y
authors: Shiratori
authors: M
authors: M
authors: Omata
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D004268:DNA-Binding Proteins; D016368:Frameshift Mutation; D005656:Fungal Proteins / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins