PTEN hamartoma tumor syndromes

Eur J Hum Genet. 2008 Nov;16(11):1289-300. doi: 10.1038/ejhg.2008.162. Epub 2008 Sep 10.


The PTEN hamartoma tumor syndromes (PHTS) are a collection of rare clinical syndromes characterized by germline mutations of the tumor suppressor PTEN. These syndromes are driven by cellular overgrowth, leading to benign hamartomas in virtually any organ. Cowden syndrome (CS), the prototypic PHTS syndrome, is associated with increased susceptibility to breast, thyroid, and endometrial cancer. PTEN is located on chromosome 10q22-23 and negatively regulates the prosurvival PI3K/Akt/mTOR pathway through its lipid phosphatase activity. Loss of PTEN activates this pathway and leads to increased cellular growth, migration, proliferation, and survival. Clinical management of patients with PHTS, particularly those with CS, should include early and frequent screening, surveillance, and preventive care for associated malignancies. Concomitant with improved understanding of the biology of PTEN and the PI3K/Akt/mTOR pathway, inhibitors of this pathway are being developed as anticancer agents. These medications could have applications for patients with PHTS, for whom no medical options currently exist.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Chromosomes, Human, Pair 10 / genetics
  • Chromosomes, Human, Pair 10 / metabolism
  • Female
  • Hamartoma Syndrome, Multiple* / drug therapy
  • Hamartoma Syndrome, Multiple* / genetics
  • Hamartoma Syndrome, Multiple* / metabolism
  • Humans
  • Male
  • Mutation*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases


  • Antineoplastic Agents
  • Protein Kinases
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human