PTEN

The PTEN gene provides instructions for making a protein that is found in almost all tissues in the body. This protein acts as a tumor suppressor, which means that it helps regulate the cycle of cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. The PTEN protein modifies other proteins and fats (lipids) by removing phosphate groups, which consist of three oxygen atoms and one phosphorus atom. Based on this activity, the PTEN protein is a type of enzyme called a phosphatase.

The PTEN enzyme acts as part of a chemical pathway that signals cells to stop dividing and triggers cells to undergo a form of programmed cell death called apoptosis. These functions prevent uncontrolled cell growth that can lead to the formation of tumors. Evidence also suggests that the PTEN enzyme helps control cell movement (migration), the sticking (adhesion) of cells to surrounding tissues, and the formation of new blood vessels (angiogenesis). Additionally, the enzyme likely plays a role in maintaining the stability of a cell's genetic information.

Cowden syndrome - caused by mutations in the PTEN gene

Researchers have identified more than 100 mutations in the PTEN gene that can cause Cowden syndrome. These genetic changes are often inherited from a parent and affect all of the body's cells. Mutations in the PTEN gene include changes in a small number of DNA building blocks (base pairs) and, in some cases, deletions of a large number of base pairs from the gene. PTEN mutations lead to the production of an enzyme that does not function properly or does not work at all. The defective enzyme is unable to restrain cell division or signal abnormal cells to die, which can contribute to the development of noncancerous growths called hamartomas and cancerous tumors.

breast cancer - increased risk from variations of the PTEN gene

Changes in the PTEN gene increase the risk of developing breast cancer as part of a rare inherited cancer syndrome called Cowden syndrome. These inherited mutations are thought to account for only a small fraction of all breast cancer cases.

other disorders - caused by mutations in the PTEN gene

Mutations in the PTEN gene cause several other disorders that are characterized by the development of noncancerous tumor-like growths called hamartomas. These disorders include Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome. Together, these disorders are called PTEN hamartoma tumor syndromes (PHTS). The mutations responsible for these syndromes are present in all of the body's cells and are often inherited from a parent. Some of these mutations lead to a defective version of the PTEN enzyme that cannot perform its function as a tumor suppressor. Other mutations prevent the PTEN gene from producing any enzyme at all. Without the PTEN enzyme, cells can divide in an uncontrolled way and damaged cells continue to divide inappropriately, leading to the development of hamartomas.

Researchers have also identified PTEN mutations in several people who have both an unusually large head size (macrocephaly) and the characteristic features of autism, a developmental disorder that affects communication and social interaction. Many of these mutations change single protein building blocks (amino acids) in the PTEN enzyme or lead to the production of an abnormally short version of the enzyme. It is unclear how changes in the PTEN gene are related to the risk of developing autism. Some of these mutations have also been reported in families with Cowden syndrome and other PTEN hamartoma tumor syndromes.

other cancers - associated with the PTEN gene

Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the PTEN gene are among the most common genetic changes found in human cancers. These mutations occur only in tumor cells.

Studies suggest that the PTEN gene may be the most frequently mutated gene in prostate cancer and in cancer of the uterine lining (endometrial cancer). PTEN mutations also have been identified in several other types of cancer, including certain aggressive brain tumors (glioblastomas and astrocytomas) and an aggressive form of skin cancer called melanoma. Mutations in the PTEN gene result in an altered enzyme that has lost its tumor suppressor function. The loss of this enzyme likely permits certain cells to divide uncontrollably, contributing to the growth of cancerous tumors. In some cases, the presence of PTEN mutations is associated with more advanced stages of tumor growth.