Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer

J Clin Oncol. 2010 Aug 10;28(23):3770-8. doi: 10.1200/JCO.2009.27.0215. Epub 2010 Jul 12.


Purpose: To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development.

Patients and methods: The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node-negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer.

Results: Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) - positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2.

Conclusion: Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy
  • Chromosomes, Human, Pair 1 / genetics*
  • Disease Models, Animal
  • Female
  • Gene Dosage
  • Gene Expression
  • Genetic Predisposition to Disease
  • Humans
  • Mice
  • Neoplasm Recurrence, Local
  • Period Circadian Proteins / genetics*
  • Prognosis
  • Receptors, Estrogen
  • Sequence Deletion
  • Survival Analysis


  • PER3 protein, human
  • Period Circadian Proteins
  • Receptors, Estrogen