PTEN hamartoma-tumour syndromes

PTEN hamartoma-tumour syndromes

A group of rare clinical syndromes that share germline mutations of the tumour suppressor PTEN and are characterised by cell overgrowth, leading to hamartomas in virtually any organ. PTEN is located on chromosome 10q22-23 and encodes a protein that negatively regulates the prosurvival PI3K/Akt/mTOR pathway, acting as a lipid phosphatase. Loss of PTEN activates the PI3K/Akt/mTOR pathway and leads to increased cell growth, migration, proliferation and survival.

Molecular pathology
Cowden syndrome, the prototypic PTEN hamartoma-tumour syndrome (PHTS), carries an increased risk of breast, thyroid and endometrial cancer; all patients with PHTS should have early and frequent screening, surveillance and preventive care for associated malignancies. PI3K/Akt/mTOR pathway inhibitors are being developed as anticancer agents.

PTEN hamartoma-tumour syndromes
• Cowden syndrome;
• Juvenile polyposis;
• Peutz-Jeghers syndrome;
• Proteus syndrome;
• Proteus-like syndrome.