PMS2

The PMS2 gene provides instructions for making a protein that plays an essential role in repairing DNA. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The PMS2 protein joins with the MLH1 protein to form an active protein complex. This protein complex coordinates the activities of other proteins that repair mistakes made during DNA replication. Repairs are made by removing the section of DNA that contains mistakes and replacing it with a corrected DNA sequence. The PMS2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.

Lynch syndrome - increased risk from variations of the PMS2 gene

Mutations in the PMS2 gene have been reported in about 2 percent of families with Lynch syndrome that have an identified gene mutation. PMS2 mutations cause the production of an abnormally short or inactivated PMS2 protein that cannot efficiently repair mistakes made during DNA replication. 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.

Mutations in the PMS2 gene sometimes cause a variant of Lynch syndrome called Turcot syndrome. In addition to colorectal cancer, people with Turcot syndrome tend to develop a particular type of brain tumor called a glioblastoma.

other cancers - caused by mutations in the PMS2 gene

Some individuals in families affected by Lynch syndrome have a mutation in both copies of the PMS2 gene. Most often, the same mutation occurs in both copies of the gene (a homozygous mutation) in each cell. People with a homozygous PMS2 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 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.