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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 2001 Jun;92(6):587–591. doi: 10.1111/j.1349-7006.2001.tb01134.x

Frameshift Mutations at Mononucleotide Repeats in RAD50 Recombinational DNA Repair Gene in Colorectal Cancers with Microsatellite Instability

Tsuneo Ikenoue 1,2,✉, Goichi Togo 1, Keiichi Nagai 3, Hideaki Ijichi 1, Jun Kato 1, Yutaka Yamaji 1, Makoto Okamoto 1, Naoya Kato 1, Takao Kawabe 1, Atsushi Tanaka 2, Masayuki Matsumura 2, Yasushi Shiratori 1, Masao Omata 1
PMCID: PMC5926751  PMID: 11429044

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.

Keywords: Microsatellite instability, Frameshift mutation, RAD50, Recombinational DNA repair, Colorectal cancer

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