Open AccessFrameshift Mutations at Mononucleotide Repeats in RAD50 Recombinational DNA Repair Gene in Colorectal Cancers with Microsatellite Instability
Author(s) -
Ikenoue Tsuneo,
Togo Goichi,
Nagai Keiichi,
Ijichi Hideaki,
Kato Jun,
Yamaji Yutaka,
Okamoto Makoto,
Kato Naoya,
Kawabe Takao,
Tanaka Atsushi,
Matsumura Masayuki,
Shiratori Yasushi,
Omata Masao
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01134.x
Subject(s) - frameshift mutation , microsatellite instability , rad50 , biology , carcinogenesis , genetics , dna mismatch repair , dna repair , colorectal cancer , cancer research , gene , genome instability , mutation , cancer , dna , microsatellite , dna damage , dna binding protein , transcription factor , allele
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.