When Overgrowth Bumps Into Cancer: The PTEN-Opathies



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    • Jessica Mester, M.S. is a certified genetic counselor and coordinator of several PTEN research studies and of the PTEN/Cowden Multidisciplinary Clinic, all housed at the Cleveland Clinic. She is the author or coauthor of 13 peer reviewed original publications describing PTEN-opathies and their implications in clinical and genetic counseling care.

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    • Correspondence to: Charis Eng, M.D., Ph.D., FACP, 9500 Euclid Ave. NE50, Cleveland, OH 44195. E-mail: engc@ccf.org

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    • Charis Eng, M.D., Ph.D., FACP a member of the Institute of Medicine of the US National Academies of Sciences, is the Sondra J. and Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine, the founding chairwoman of the Cleveland Clinic Genomic Medicine Institute and founding director of its clinical component, the Center for Personalized Genetic Healthcare. She is PI of several PTEN-related research studies and is the Medical Director of the PTEN/Cowden Multidisciplinary Clinic at the Cleveland Clinic. She and her team mapped and identified PTEN as the causative gene for Cowden syndrome, and subsequently, among her almost 400 original peer-reviewed publications are those elucidating the clinical spectrum of germline PTEN mutations and their function. She recently coined the term PTEN-opathy to encompass those syndromes whose mutation define the PTEN signaling pathway, including AKT1 and PIK3CA, for PTEN mutation negative Cowden syndrome.

  • Conflicts of interest: nothing to declare.
  • Correction added on 12th July 2017, after initial online publication. A duplicate of this article was published under the DOI 10:1002/j.1552-4876.2013.31364.x. This duplicate has now been deleted and its DOI redirected to this version of the article.


PTEN is a dual-specificity phosphatase and well-known tumor suppressor gene. When functioning properly, it works in its canonical pathway to inhibit AKT/mTOR and MAPK signaling, leading to cell death and growth regulation. PTEN mutations cause dysregulation of these pathways, resulting in cellular proliferation and overgrowth. When germline mutations are present as in patients with PTEN Hamartoma Tumor Syndrome (PHTS), benign and malignant neoplasias occur as well as cerebral overgrowth and neurodevelopmental abnormalities. This review article will summarize recent laboratory and clinical investigations relating to PTEN, highlighting the overgrowth aspects of this syndrome and the molecular drivers behind these key phenotypes. Finally, therapies developed targeted the PI3K/AKT/mTOR pathway for other tumor predisposition syndromes will be discussed. © 2013 Wiley Periodicals, Inc.