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Most bowel cancers with a broken DNA spell-checker have not mutated the gene at all: they have switched it off chemically. Removing the chemical tag in the laboratory turned the gene, and the repair system, back on.
Hypermethylation of the 5' CpG island of hMLH1 was found in the majority of sporadic primary colorectal cancers with microsatellite instability, and was often though not invariably associated with loss of hMLH1 protein expression. Methylation also occurred, less commonly, in microsatellite-stable tumours and in unstable tumours with known mismatch repair gene mutations; no hypermethylation of hMSH2 was found. In cell lines with microsatellite instability, reversal of methylation with 5-aza-2'-deoxycytidine restored hMLH1 protein expression and mismatch repair capacity.
It established the epigenetic route to mismatch repair deficiency, which is why an MLH1-deficient tumour is tested for MLH1 methylation or BRAF V600E before a family is told it may have Lynch syndrome.
Shares MLH1, MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Lynch syndrome.
Shares Kenneth W. Kinzler, Bert Vogelstein, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares Kenneth W. Kinzler, Bert Vogelstein, Mismatch repair & microsatellite instability, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center.
Shares MLH1, MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares MLH1, MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Lynch syndrome.
Shares MLH1, MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Lynch syndrome.
Shares MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares MSI and mismatch-repair testing, dMMR (mismatch repair deficiency by IHC), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.