Article open access publication

Cancer risk and genotype–phenotype correlations in PTEN hamartoma tumor syndrome

Familial Cancer, Springer Nature, ISSN 1389-9600

Volume 13, 1, 2014

DOI:10.1007/s10689-013-9674-3, Dimensions: pub.1033986037, PMID: 23934601,



  1. (1) The Netherlands Foundation for the Detection of Hereditary Tumors, Rijnsburgerweg 10, Poortgebouw Zuid, 2333 AA, Leiden, The Netherlands
  2. (2) Radboud University Nijmegen Medical Centre, grid.10417.33
  3. (3) Mayo Clinic, grid.66875.3a
  4. (4) St Mary's Hospital, grid.416523.7
  5. (5) Laboratoire d’ Oncogénétique et Angiogénétique Moléculaire, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hopitaux de Paris, Université Pierre et Marie Curie, Paris, France
  6. (6) Oslo University Hospital, grid.55325.34
  7. (7) Leiden University Medical Center, grid.10419.3d
  8. (8) Department of Clinical Genetics, St Georges, University of London, London, UK
  9. (9) University Medical Center Groningen, grid.4494.d
  10. (10) Institute of Human Genetics, University Hospital Bonn, Bonn, Germany
  11. (11) University of Basel, grid.6612.3
  12. (12) Maastricht University Medical Centre, grid.412966.e
  13. (13) Newcastle University, grid.1006.7
  14. (14) Hunter Family Cancer Service, Newcastle upon Tyne, NSW, Australia
  15. (15) St Vincent’s Hereditary Cancer Service, Sydney, Australia
  16. (16) UNSW Sydney, grid.1005.4
  17. (17) University of Copenhagen, grid.5254.6, KU
  18. (18) Mayo Clinic, grid.417468.8


Patients with germline PTEN mutations are at high risk of developing benign and malignant tumours. We aimed to evaluate the cumulative risk of several types of cancer and of dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease, LDD). In addition, genotype-phenotype correlations in PTEN hamartoma tumour syndrome (PHTS) were assessed. Data on patients with PTEN mutations were collected from clinical genetic centres in Western Europe, Australia, and the USA. The cumulative risk of developing cancers of the breast, thyroid, endometrium, skin, kidneys, colorectum, and lungs, and also LDD was calculated by Kaplan-Meier methods. Associations between mutations and cancer were assessed by Chi square means. A total of 180 germline PTEN mutation carriers, 81 males (45%), from nine countries were included. The cumulative risk of developing any cancer and/or LDD at age 60 was 56% for males and 87% for females (p = 0.001). Females had significant higher risks of developing breast cancer, thyroid cancer, and LDD than males. The only genotype-phenotype correlation identified was a lower frequency of thyroid cancer in patients with missense mutations (p = 0.014). In conclusion, PHTS patients, particularly females, have a substantial risk of developing one or more tumours from a broad tumour spectrum. Major genotype-phenotype associations could not be identified.

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