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

Joan Climent, Jesus Perez-Losada, David A. Quigley, Il Jin Kim, Reyno Delrosario, Kuang-Yu Jen, Ana Bosch, Ana Lluch, Jian Hua Mao, Allan Balmain

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3770-3778
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number23
DOIs
StatePublished - Aug 10 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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