MSH6

The MSH6 gene provides instructions for making a protein that plays an essential role in repairing DNA. This protein fixes mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH6 protein joins with another protein, the MSH2 protein, to form an active protein complex. This active protein complex identifies places on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1-PMS2 protein complex, then takes over to help with the actual repair. The MSH6 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

Lynch syndrome - increased risk from variations of the MSH6 gene

Mutations in the MSH6 gene have been reported in about 10 percent of families with Lynch syndrome that have an identified gene mutation. All of these mutations cause the production of an abnormally short, nonfunctional MSH6 protein or a partially active version of the protein. When the MSH6 protein is absent or ineffective, the number of mistakes that are left unrepaired during cell division increases substantially. If the cells continue to divide, errors accumulate in DNA; the cells become unable to function properly and may form a tumor in the colon or another part of the body.

People with mutations in the MSH6 gene also have an increased risk of developing cancers of the ovary, stomach, small intestine, liver, gallbladder duct, upper urinary tract, brain, and skin.

other cancers - caused by mutations in the MSH6 gene

Some individuals in families affected by Lynch syndrome have a mutation in both copies of the MSH6 gene. Most often, the same mutation occurs in both copies of the gene (a homozygous mutation) in each cell. People with a homozygous MSH6 mutation have a syndrome distinct from Lynch syndrome. In addition to colorectal cancer, they may develop cancers of the blood (leukemia or lymphoma). Some of these individuals will also develop particular types of noncancerous tumors that grow along nerves (neurofibromas) and have light brown patches of skin called café-au-lait spots. These two signs are characteristic of a condition known as neurofibromatosis. The onset of colon cancer in these individuals is extremely early, often occurring during childhood. This syndrome involving colon cancer, leukemia or lymphoma, and neurofibromatosis is sometimes called CoLoN.