"Modification" type microsatellite instability is correlated with p53 mutation in sporadic colorectal cancer / 肿瘤研究与临床

ABSTRACT

Objective High frequency microsatellite instability(MSI-H)was considered to be the phenotype of DNA mismatch repair(MMR)deficiency.However,a contradiction was noticed that p53 mutation is reposed to be extremely rare in MSI-H tumors.The aim of the current study was to confirm and try to explain this a phenomenon.We have demonstrated a direct link between MMR model and"modification"type MSI,and suggested the new categorization system of MSI by quantification of MSI profile.Based on this categorization system we studied the relationship between MSI and mutation of p53 oncogene in colorectal cancer.Methods A series of 180 sporadic colorectal cancer cases were investigated for their microsatellite status and p53 mutations.High resolution fluorescent microsatellite instability analysis assay and direct sequencing were employed in this study.Results Two definite patterns of microsatellite instability were confirmed,i.e."modification" type and "jumping" type MSI. In colorectal cancer,low frequency microsatellite instability (MSI-L)cases all showed pure"modification"type,while"jumping"type MSI changes were confirmed in all MSI-H cases.MSI-H was related with proximal tumor location and poorly differentiated.p53 mutation rate was more frequent in well differentiated tumors.Interestingly.MSI-L tumor showed a 40% mutation rate which is similar with MSS tumor 41%,however,in MSI-H tumors no p53 mutation was confirmed.Conclusions We confirm in human colorectal cancers,the"modification"type MSI might be connected with MMR defection.The mechanism underlying MSI-H phenotype was supposed to be other than MMR deficiency.