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PTEN hamartoma tumor syndrome: clinical risk assessment and management protocol
1Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA; Division of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore; Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore 169610, Singapore.
Abstract:
The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important phosphatase that counteracts one of the most critical cancer pathways: the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathways. Clinically, deregulation of PTEN function resulting in reduced PTEN expression and activity is implicated in human diseases. Cowden syndrome (CS) is an autosomal dominant disorder characterized by benign and malignant tumors. CS-related individual features occur commonly in the general population. Approximately 25% of patients diagnosed with CS have pathogenic germline PTEN mutations, which increase lifetime risks of breast, thyroid, uterine, renal and other cancers. PTEN testing and intensive cancer surveillance allow for early detection and treatment of these cancers for mutation positive patients and their relatives. In this review, we highlight our current knowledge of germline PTEN mutations in relation to human disease. We review current clinical diagnosis and management recommendations for PHTS including recent discoveries in understanding PTEN function regulation and how this can be exploited therapeutically.
Insights
Germline PTEN mutations are linked to Cowden syndrome and increase cancer risks. Early PTEN testing and surveillance aid in detecting and treating associated cancers, improving patient outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a crucial tumor suppressor.
- PTEN counteracts the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, a critical pathway in cancer.
- Deregulation of PTEN is implicated in various human diseases, including Cowden syndrome (CS).
Purpose of the Study:
- To review current knowledge on germline PTEN mutations and their relation to human diseases.
- To highlight clinical diagnosis and management strategies for PTEN Hamartoma Tumor Syndrome (PHTS).
- To discuss recent discoveries in PTEN function regulation and therapeutic exploitation.
Main Methods:
- Literature review of studies on PTEN mutations, Cowden syndrome, and PHTS.
- Analysis of clinical diagnosis and management guidelines.
- Synthesis of current research on PTEN function and therapeutic targets.
Main Results:
- Approximately 25% of Cowden syndrome patients harbor pathogenic germline PTEN mutations.
- These mutations significantly increase lifetime risks for breast, thyroid, uterine, and renal cancers.
- PTEN testing and surveillance enable early cancer detection in mutation carriers.
Conclusions:
- Germline PTEN mutations are key drivers in Cowden syndrome and PHTS, necessitating genetic testing.
- Intensive cancer surveillance is vital for early detection and management of associated malignancies.
- Understanding PTEN regulation offers potential therapeutic avenues for PTEN-related disorders.
