Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats.
Bottom Line: microsatellite instability (MSI) is commonly screened using a panel of two mononucleotide and three dinucleotide repeats as recommended by a consensus meeting on MSI tumours held at the National Cancer Institute (Bethesda, MD, USA).Several studies have confirmed the sensitivity, specificity and ease of use of the pentaplex panel; however, its sensitivity for the detection of MSH6-deficient tumours is so far unknown.MSI-H status was confirmed in 15 out of 15 (100%) cases where matching normal DNA was available and in 28 out of 29 (97%) cases where matching DNA was not available or was not analysed. these results show that the pentaplex assay efficiently discriminates the MSI status of tumours with an MSH6 defect.
Affiliation: INSERM, UMRS 938-Centre de Recherche Saint-Antoine, Equipe 'Instabilité des Microsatellites et Cancers', 184 rue du Faubourg Saint-Antoine, Paris F-75012, France.Show MeSH
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Mentions: The size of all PCR products was determined individually using Genescan software and was rounded up or down to the next integer. Amplification for all five markers was achieved in 23 out of 25 (92%) of the normal tissue samples. The size variation observed was 103–105 bp (NR-21), 116–118 bp (BAT-26), 122–124 bp (BAT-25), 130–131 bp (NR-24) and 141–142 bp (NR-22). These values define the quasi-monomorphic variation range (QMVR) for each marker in the germline DNA analysed in this study. They are slightly different from the values reported in our original manuscript. We have already shown that this is due to the use of different instrumentation and reagents (Buhard et al, 2006). These factors were not identical 8 years apart. The total variation range (TVR) as defined by the sum of the sizes of the five markers was 613–619 bp for normal DNA in the present analysis (Figure 2). None of the markers in any of the individuals in this study showed an allelic variant that was clearly outside of the QMVR. This has been found on rare occasions in the worldwide populations (Buhard et al, 2006). Although the ethnic origin of the Dutch patients analysed here was unknown, the majority were likely to be Caucasian. If present in a series, variant alleles should not be included for QMVR and TVR calculation in normal DNA.
Affiliation: INSERM, UMRS 938-Centre de Recherche Saint-Antoine, Equipe 'Instabilité des Microsatellites et Cancers', 184 rue du Faubourg Saint-Antoine, Paris F-75012, France.