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

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

Author information

  • 1Helen Diller Family Comprehensive Cancer Center, Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

Abstract

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.

PMID:
20625127
[PubMed - indexed for MEDLINE]
PMCID:
PMC2917310
Free PMC Article
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