In order to assess whether variations affecting DNA mismatch repair (MMR) genes are pathogenic and hence predisposing to Lynch syndrome (LS), a three-step assessment model has been proposed. Where LS is suspected based on family history, STEP1 is dedicated to the identification of the causative MMR gene and the variation within it. Thereafter, in STEP2 of… (More)
Lynch syndrome (LS) is associated with germline mutations in DNA mismatch repair (MMR) genes. The first “hit” to inactivate one allele of the predisposing MMR gene is present in every cell, contributing to accelerated tumorigenesis. Less information is available of the nature, timing, and order of other molecular “hits” required for tumor development. To… (More)
BACKROUND: The target substrates of DNA mismatch recognising factors MutSa (MSH2 þ MSH6) and MutSb (MSH2 þ MSH3) have already been widely researched. However, the extent of their functional redundancy and clinical substance remains unclear. Mismatch repair (MMR)-deficient tumours are strongly associated with microsatellite instability (MSI) and the degree… (More)
Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in the Western world and interactions between genetic and environmental factors, including diet, are suggested to play a critical role in its etiology. We conducted a long-term feeding experiment in the mouse to address gene expression and methylation changes arising in… (More)
3 " There is nothing, Sir, too little for so little a creature as man. It is by studying little things that we attain the great art of having as little misery and as much happiness as possible. "