<P><B>Summary</B></P><P>Parts of gastric (GC) and colorectal cancers (CRC) exhibit microsatellite instability (MSI) that causes frameshift mutations and contributes to cancer development. DNA replication and repair play c...
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https://www.riss.kr/link?id=A107576003
2010
-
RFC3 ; MSI ; Mutation ; Expression ; Gastric cancer ; Colorectal cancer
SCI,SCIE,SCOPUS
학술저널
1431-1437(7쪽)
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P><B>Summary</B></P><P>Parts of gastric (GC) and colorectal cancers (CRC) exhibit microsatellite instability (MSI) that causes frameshift mutations and contributes to cancer development. DNA replication and repair play c...
<P><B>Summary</B></P><P>Parts of gastric (GC) and colorectal cancers (CRC) exhibit microsatellite instability (MSI) that causes frameshift mutations and contributes to cancer development. DNA replication and repair play crucial roles in maintenance of genome stability, and their alterations contribute to cancer development. In this study, we analyzed mutation of RFC1 and RFC3, clamp loaders in DNA replication, in GC and CRC with MSI. We analyzed mononucleotide repeats in <I>RFC1</I> and <I>RFC3</I> in 29 GC with high MSI (MSI-H), 20 GC with low MSI (MSI-L), 45 GC with stable MSI (MSS), 35 CRC with MSI-H, 20 CRC with MSI-L, and 45 CRC with MSS by single-strand conformation polymorphism. We also analyzed RFC3 expression in the GC and CRC. We found <I>RFC3</I> frameshift mutations in 7 GC (24.1%) and 9 CRC with MSI-H (25.7%) but not in cancers with MSI-L or MSS. The mutations consisted of 14 c.244delA, one 243_244delAA, and one c.244dupA, which would result in premature stops of RFC3 amino acid synthesis. Loss of RFC3 expression was observed in 51% of the GC and 65% of the CRC, but all of the cancers with <I>RFC3</I> frameshift mutations were weak or negative. Our data indicate <I>RFC3</I> mutation and loss of RFC3 expression occur in large fractions of GC and CRC and suggest that these alterations may contribute to the cancer pathogenesis by deregulating DNA repair and replication.</P>