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

Marry H. Nieuwenhuis, C. Marleen Kets, Maureen Murphy-Ryan, Helger G. Yntema, D. Gareth Evans, Chrystelle Colas, Pal Møller, Frederik J. Hes, Shirley V. Hodgson, Maran J.W. Olderode-Berends, Stefan Aretz, Karl Heinimann, Encarna B. Gómez García, Fiona Douglas, Allan Spigelman, Susanne Timshel, Noralane M. Lindor, Hans F.A. Vasen

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)57-63
Number of pages7
JournalFamilial Cancer
Issue number1
StatePublished - Mar 2014


  • Multiple hamartoma syndrome
  • Neoplasms
  • PTEN phosphohydrolase

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Genetics(clinical)
  • Cancer Research


Dive into the research topics of 'Cancer risk and genotype-phenotype correlations in PTEN hamartoma tumor syndrome'. Together they form a unique fingerprint.

Cite this