Important microsatellite markers in the investigation of replication errors (RER) in colorectal carcinomas.

Abstract

DNA replication errors (RER) have been found in hereditary nonpolyposis colorectal carcinomas and in sporadic colorectal carcinomas. The incidence of RER depends on which and how many markers are examined. The main purpose of the present study was to determine the key markers for detecting RER most efficiently. The RER status of 76 sporadic advanced colorectal carcinomas in the proximal colon were investigated. Seven microsatellite markers (D2S123, D3S1029, D3S1611, D2S72, TP53, Mfd26 and BAT26) were chosen to determine the RER status by PCR using the non-Rl method, because these seven markers have frequently been used in other studies and also detect RER. It was found that 44.7% of sporadic colorectal advanced carcinomas in the proximal colon (34 of 76) showed RER at one or more loci. Among these 34 cases, RER was present at three or more markers (severe RER) in 22. All 22 of these cases showed RER at BAT26 and TP53. The other 12 cases with RER showed RER at one or two markers (mild RER). Eleven of these 12 cases (91%) showed RER at Mfd26 and there were one or two cases with mild RER at each of the other loci. When one intends to analyze routinely a large number of cases, an analysis of two or three markers (Mfd26 and BAT26 or TP53) is considered to be sufficient for detecting mild and severe RER.