KLLN

Cowden syndrome

Some cases of Cowden syndrome and a similar condition called Cowden-like syndrome result from a change involving the KLLN gene. These conditions are characterized by multiple tumor-like growths called hamartomas and an increased risk of developing certain cancers. When Cowden syndrome and Cowden-like syndrome are caused by KLLN gene mutations, the conditions are associated with a particularly high risk of developing breast and kidney cancers.

The genetic change associated with these conditions is known as promoter hypermethylation. The promoter is a region of DNA near the gene that controls gene activity (expression). Hypermethylation occurs when too many small molecules called methyl groups are attached to the promoter region. The extra methyl groups reduce the expression of the KLLN gene, which means that less killin is produced. A reduced amount of killin may allow abnormal cells to survive and proliferate inappropriately, which can lead to the formation of tumors.

The promoter region of the KLLN gene is shared with another gene, PTEN. The single promoter controls the expression of both genes. However, specific hypermethylation of the KLLN gene promoter only affects the expression of the KLLN gene; people with this type of genetic change have normal expression of the PTEN gene. Other types of mutations in the PTEN gene can cause Cowden syndrome and Cowden-like syndrome.