Cancer PTEN is one of the most commonly lost
tumor suppressors in human cancer; up to 70% of men with prostate cancer are estimated to have lost a copy of the
PTEN gene at the time of diagnosis. A number of studies have found increased frequency of
PTEN loss in tumours which are more highly visible on diagnostic scans such as
mpMRI, potentially reflecting increased
proliferation and cell density in these tumours. During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Frequent genetic inactivation of PTEN occurs in
glioblastoma,
endometrial cancer, and
prostate cancer; and reduced expression is found in many other tumor types such as lung and breast cancer. Furthermore,
PTEN mutation also causes a variety of inherited predispositions to cancer.
Non-cancerous neoplasia Researchers have identified more than 70
mutations in the
PTEN gene in people with
Cowden syndrome. These mutations can be changes in a small number of
base pairs or, in some cases, deletions of a large number of base pairs. Most of these mutations cause the
PTEN gene to make a protein that does not function properly or does not work at all. The defective protein is unable to stop cell division or signal abnormal cells to die, which can lead to tumor growth, particularly in the
breast,
thyroid, or
uterus. Mutations in the
PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of non-cancerous tumors called
hamartomas. These disorders include
Bannayan–Riley–Ruvalcaba syndrome and
Proteus-like syndrome. Together, the disorders caused by
PTEN mutations are called
PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be non-functional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors. When defective, PTEN protein interacts with the protein of a second gene known as
Tp53 to dampen energy production in neurons. This severe stress leads to a spike in harmful mitochondrial DNA changes and abnormal levels of energy production in the cerebellum and hippocampus, brain regions critical for social behavior and cognition. When PTEN protein is insufficient, its interaction with
p53 triggers deficiencies and defects in other proteins that also have been found in patients with
learning disabilities including
autism. Patients with defective
PTEN can develop cerebellar mass lesions called dysplastic gangliocytomas or
Lhermitte–Duclos disease. ==As a drug target==