Optimising methods for determining RER status in colorectal cancers

Approximately 13% of colorectal cancers display microsatellite instability (MSI), a form of replication error repair. Colorectal cancers developing in individuals with constitutional defects in the mismatch repair (MMR) genes hMLH1, hMSH2, hPMS1 and hPMS2 consistently show evidence of this phenomeno n. Since MSI is indicative of MMR deficiency, testing colorectal cancers fo r MSI provides a method of refining the identification of carriers of germl ine MMR mutations. To assess which microsatellites represent the best repor ters of replication error (RER) status we have examined 116 early onset col orectal cancers for MSI. MSI was assessed using eight dinucleotide-and two mononucleotide-repeat fluorescently labelled polymerase chain reaction (PCR ) markers. The two mononucleotide repeat markers (BAT25 and BAT26) were hig hly sensitive and typing of either represents an efficient strategy for def ining RER status of colorectal cancers and obviates the requirement of typi ng numerous microsatellite markers. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.