The PTEN gene plays a foundational role in the human body, acting as a tumor suppressor. It provides the blueprint for an enzyme found in nearly all tissues, which helps regulate various cellular processes.
The Role of the PTEN Gene
The primary function of the PTEN gene is to act as a tumor suppressor. It helps regulate cell division. This regulation is achieved by its activity as a phosphatase, an enzyme that removes phosphate groups from other molecules.
PTEN specifically acts on a key signaling pathway within cells known as the PI3K/AKT pathway. This pathway promotes cell growth, proliferation, and survival. By removing a phosphate group from phosphatidylinositol-3,4,5-trisphosphate (PIP3), PTEN reduces its levels. This action promotes programmed cell death, known as apoptosis, and can halt the cell cycle.
PTEN Gene Mutations
A PTEN gene mutation is a change in its DNA sequence that can impair or eliminate its normal tumor suppressor function. These mutations are categorized by how they arise and where they are found in the body.
A germline mutation is an alteration inherited from a parent, present in virtually all body cells, and can be passed down to offspring. In contrast, a somatic mutation is acquired during a person’s lifetime. These mutations occur only in specific cells, such as those within a tumor.
Associated Health Conditions
Germline mutations in the PTEN gene are associated with PTEN Hamartoma Tumor Syndrome (PHTS), an umbrella term for distinct but overlapping disorders like Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Individuals with PHTS typically develop multiple benign growths called hamartomas, which are disorganized but non-cancerous collections of cells.
Cowden syndrome is characterized by mucocutaneous lesions, such as trichilemmomas (benign hair follicle tumors) and papillomatous papules, along with macrocephaly (larger than average head size). Bannayan-Riley-Ruvalcaba syndrome often presents congenitally or in childhood with macrocephaly, intestinal polyposis (multiple polyps in the intestines), lipomas (benign fatty tumors), and vascular malformations. The lifetime risk of developing breast cancer for individuals with a PTEN germline variant can be as high as 85%, with an average age of diagnosis between 38 and 46 years.
Beyond breast cancer, individuals with PTEN mutations also have an increased risk for several other cancers, including thyroid cancer (especially follicular type), endometrial cancer, kidney (renal cell) cancer, and colorectal cancer. There is also a recognized link between PTEN mutations and neurodevelopmental conditions. A subset of individuals with PTEN mutations, particularly those with macrocephaly, may be diagnosed with autism spectrum disorder (ASD).
Genetic Testing and Screening
Genetic testing for the PTEN gene is available for individuals suspected of having a PTEN-related condition. Candidates for this testing include those with a personal or family history suggestive of PHTS, such as multiple primary cancers or characteristic benign growths. Women presenting with multiple distinct cancers may also be considered for testing.
The testing process typically involves obtaining a sample of DNA, often from a blood or saliva sample. This sample is then analyzed to look for specific alterations in the PTEN gene sequence. Identifying a germline PTEN mutation can confirm a diagnosis of PHTS and inform individuals about their inherited risk for associated health issues.
Managing PTEN-Related Risks
Following a diagnosis of a PTEN mutation, a comprehensive management and surveillance plan is established to address the increased health risks. This proactive approach aims to detect potential issues, particularly cancers, at their earliest and most treatable stages. Regular medical check-ups and specialized screenings become a routine part of care.
For instance, guidelines recommend increased cancer surveillance, such as earlier and more frequent mammograms and breast MRIs for breast cancer screening, often starting around age 30. Thyroid ultrasounds are typically recommended annually, and colonoscopies may begin earlier than general population guidelines, sometimes around age 35-45, and be repeated every five years. Regular dermatological examinations are also advised to monitor for skin lesions, and physical examinations help identify any new or changing symptoms.