Abstract
RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)9 at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs may be a cellular response against tumor from further progression, while hRAD50 mutation may be involved in the development of MSI CRCs.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide
A frameshift mutation at mononucleotide repeats (A)9 between codon 719 and 722 in human RAD50 (hRAD50) has been found in microsatellite instability (MSI) human tumors including CRCs, but not in microsatellite stable (MSS) tumors [6,7,8], indicating that the frameshift mutation of hRAD50 may play a role in the tumorigenesis of MSI CRCs
These results suggest the tumor suppressor function of hRAD50 and that the mutation that impairs hRAD50 expression may contribute to development and progression of MSI CRCs
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide. It is generally accepted that CRC develops from two different pathways: chromosomal instability and microsatellite instability (MSI) pathway [1]. A frameshift mutation at mononucleotide repeats (A) between codon 719 and 722 in hRAD50 has been found in MSI human tumors including CRCs, but not in microsatellite stable (MSS) tumors [6,7,8], indicating that the frameshift mutation of hRAD50 may play a role in the tumorigenesis of MSI CRCs. It has been demonstrated that this mutation was related to reduced protein expression and defective non-homologous end joining activity in vitro [9]. It has been demonstrated that this mutation was related to reduced protein expression and defective non-homologous end joining activity in vitro [9] Together, these results suggest the tumor suppressor function of hRAD50 and that the mutation that impairs hRAD50 expression may contribute to development and progression of MSI CRCs. hRAD50 expression during CRC development, especially in MSI versus MSS patients, and its clinicopathological significance, has not been yet studied. We investigated hRAD50 protein expression in primary CRC, along with the corresponding distant normal mucosa, adjacent normal mucosa and lymph node metastasis, and the frameshift mutation between codon 719 and 722 in hRAD50 in CRC as well as their relationships with microsatellite status, biological and clinicopathological variables
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
