Germline mutations in PTEN are an infrequent cause of genetic predisposition to breast cancer

Oncogene. 1998 Aug 13;17(6):727-31. doi: 10.1038/sj.onc.1201984.


Heterozygous germline mutations in PTEN are responsible for most cases of Cowden Syndrome, a rare familial trait characterized by hamartomas and by predisposition to cancer of the breast and thyroid. The variable and often subtle clinical findings that characterize Cowden Syndrome are frequently unrecognized, raising the possibility that germline PTEN mutations may confer susceptibility to breast cancer in women who have not been diagnosed with this syndrome. To determine whether such mutations contribute to genetic predisposition to breast cancer within the general population, we analysed a cohort of women with early-onset breast cancer (< age 40), a subset of the population at increased risk for genetic susceptibility. Lymphoblast cell lines were analysed using either direct nucleotide sequencing (28 cases), denaturing gradient gel electrophoresis (DGGE) (34 cases) or a yeast-based truncation assay (110 cases). No definitive, truncating mutations were observed in 172 patients. Missense changes were noted in the germline of 2/60 patients analysed by direct nucleotide sequencing or DGGE, including a non-conservative amino acid substitution within the phosphatase domain, but neither showed loss of the wild-type allele in the corresponding breast tumor specimen. We conclude that germline mutations in PTEN are an uncommon cause of genetic predisposition to breast cancer within the general population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Causality
  • Cohort Studies
  • Female
  • Germ-Line Mutation*
  • Hamartoma Syndrome, Multiple / genetics
  • Humans
  • PTEN Phosphohydrolase
  • Peptide Chain Termination, Translational / genetics
  • Phosphoric Monoester Hydrolases*
  • Protein Tyrosine Phosphatases / genetics*
  • Risk Factors
  • Sequence Analysis, DNA
  • Tumor Suppressor Proteins*


  • Tumor Suppressor Proteins
  • Phosphoric Monoester Hydrolases
  • Protein Tyrosine Phosphatases
  • PTEN Phosphohydrolase
  • PTEN protein, human