PTEN is one of the most commonly lost tumor suppressors in human cancer; in fact, up to 70% of men with prostate cancer are estimated to have lost a copy of thePTEN gene at the time of diagnosis.

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.[citation needed] These mutations can be changes in a small number of base pairs or, in some cases, deletions of a large number of base pairs.[citation needed] 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.[20]

Mutations in the PTEN gene cause several other disorders that, like Cowden syndrome, are characterized by the development of non-cancerous tumors calledhamartomas. These disorders include Bannayan-Riley-Ruvalcaba syndrome and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are calledPTEN 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.[20]

Brain function and autism

Defects of the PTEN gene have been cited to be a potential cause of autism spectrum disorders.[21] 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 withp53 triggers deficiencies and defects in other proteins that also have been found in patients with learning disabilities including autism.[21]

Patients with defective PTEN can develop cerebellar mass lesions called dysplastic gangliocytomas or Lhermitte–Duclos disease.[20]

Cell regeneration

PTEN’s strong link to cell growth inhibition is being studied as a possible therapeutic target in tissues that do not traditionally regenerate in mature animals, such as central neurons. PTEN deletion mutants have recently[22] been shown to allow nerve regeneration in mice.[23]

Cell lines

Cell lines with known PTEN mutations include:

Cowden syndrome, tumor syndrome

Cowden syndrome (CS) is part of the PTEN hamartoma tumor syndrome. Hamartomas are benign, meaning noncancerous, tumor-like growths. Other clinical syndromes that are part of the PTEN hamartoma tumor syndrome are Bannayan-Riley-Ruvalcaba syndrome (BRR; diagnosed in children), Proteus syndrome, and Proteus-like syndrome. CS is characterized by a high risk of both benign and cancerous tumors of the breast, thyroid,endometrium (uterus), colorectal, kidney, and skin (melanoma).

Skin Melanoma

This slideshow requires JavaScript.

Major and minor criteria as well as the testing criteria for CS:

Major criteria:

  • Breast cancer
  • Endometrial cancer
  • Follicular thyroid cancer
  • Multiple gastrointestinal hamartomas or ganglioneuromas
  • Macrocephaly
  • Macular pigmentation of glans penis, meaning a discolored area on the skin
  • Mucocutaneous lesions
  • One biopsy-proven trichilemmoma
  • Multiple palmoplantar keratosis, meaning abnormal thickening of the hands and feet
  • Multifocal or extensive oral mucosal papillomatosis
  • Multiple cutaneous facial papules that are often verrucous, meaning wartlike projections

Minor Criteria:

  • Colon cancer
  • Esophageal glycogenic acanthosis
  • Autism-spectrum disorder
  • Mental retardation
  • Papillary or follicular variant of papillary thyroid cancer
  • Thyroid structural lesions, such as adenoma, nodule(s), goiter
  • Renal cell (kidney) carcinoma
  • Vascular anomalies, including multiple intracranial developmental venous anomalies
  • Lipomas, meaning benign soft tissue tumor
  • Single gastrointestinal hamartoma or ganglioneuroma
  • Testicular lipomatosis

Cowden Syndrome PTEN Gene Testing Criteria

  • People with a personal history of:
  • A family with a known PTEN gene mutation
  • Meeting clinical diagnostic criteria for CS
  • Bannayan-Riley-Ruvalcaba syndrome (BRR)
  • Adult Lhermitte-Duclos disease (cerebellar tumors)
  • Autism spectrum disorder and macrocephaly
  • Two or more biopsy-proben trichilemmomas
  • Two or more major criteria (one must be macrocephaly)

Source: Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. Med Genet 2000;37:828-830.

CS is suspected if a person has either three major criteria without macrocephaly, one major and three minor criteria, four minor criteria, or a relative with a clinical diagnosis of CS or BRR.

Research is ongoing to better understand CS. Approximately 80% of the people who meet the current clinical diagnosis of CS have a mutation in the PTEN gene. A blood test can determine if someone has a mutation in thePTEN gene.

Connie’s comments: Monitor your body for chronic pain or head ache, skin disorders, digestive issues and family genetic history.