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

Michael G. FitzGerald, Debbie J. Marsh, Doke Wahrer, Daphne Bell, Stacey Caron, Kristen E. Shannon, Chikashi Ishioka, Kurt J. Isselbacher, Judy E. Garber, Charis Eng, Daniel A. Haber

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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 nonconservative 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.

Original languageEnglish
Pages (from-to)727-731
Number of pages5
JournalOncogene
Volume17
Issue number6
DOIs
Publication statusPublished - 1998 Aug 13

Keywords

  • Breast cancer
  • Cowden syndrome
  • Genetic predisposition
  • PTEN/MMAC1
  • Yeast truncation assay

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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