Lockett, M.; Smale, W.; Pack, K.; Atkin, W.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA37
Academic Journal
Background: Microsatellite instability (MSI) is a change in length of a simple repeat sequence (microsatellite (MS)) in tumour DNA compared to normal. It is a non-specific marker of a mismatch repair defect. It occurs in hereditary non-polyposis CRC (HNPCC) and in a proportion of sporadic CRCs. MSI-CRCs have distinctive clinicopathological features, behaviour, and response to chemotherapy. A panel of Five MS markers is recommended for analysis of MSI in tumours, but this requires normal DNA for comparison. The use of mononucleotide markers alone (eg Bat-26) has been suggested as a simple screen for MSI without the need for normal DNA. Germline PMs in mononucleotide markers occur, and without normal DNA, may be misinterpreted as MSI. The PM rates vary according to the population studied (13-18% in African-Americans). The PM rates in the UK are not known. Aim: To determine rate of germline Bat-26 and Bat-25 PMs in a sample of the UK population. Methods: A population based sample of germline DNAs (prepared from blood) from 789 individuals from one centre of the UK flexible sigmoidoscopy screening trial was analysed. Blood DNA was amplified at Bat-25 and Bat-26 loci by polymerase chain reaction (PCR) using fluorescent labelled primers. Products were electrophoresed on 5% denaturing polyacrylamide gels on an ABI 377 sequencer and analysed using Genescan and Genotyper software. Two independent observers read the traces. Any DNAs thought to be polymorphic were re-PCRed to confirm. Results: Results were available in 787. Four (0.5%) were polymorphic at Bat-25, 1 (0.1%) at Bah26 and 0 at both loci. Conclusions: There is a Iow rate of Bat-25 and Bat-26 PMs in this UK sample. If MSI analysis was conducted on tumour DNA without matched normal tissue, about 0.6% would be incorrectly classified as MSI-positive. Bat-26 is the better marker to screen tumours for MSI as it has the lowest PM rate. MSI-positive tumours should be confirmed by comparison to normal DNA, although...


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