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 journalArticle

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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

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Gene Deletion
Estrogen Receptors
Chromosomes
Breast Neoplasms
Neoplasms
Tamoxifen
Recurrence
Gene Dosage
Circadian Rhythm
Carcinogens
Sleep
Carcinogenesis
Breast
Homeostasis
Lymph Nodes
Drug Therapy
Messenger RNA
Therapeutics
Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Climent, J., Perez-Losada, J., Quigley, D. A., Kim, I. J., Delrosario, R., Jen, K-Y., ... Balmain, A. (2010). Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. Journal of Clinical Oncology, 28(23), 3770-3778. https://doi.org/10.1200/JCO.2009.27.0215

Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. / Climent, Joan; Perez-Losada, Jesus; Quigley, David A.; Kim, Il Jin; Delrosario, Reyno; Jen, Kuang-Yu; Bosch, Ana; Lluch, Ana; Mao, Jian Hua; Balmain, Allan.

In: Journal of Clinical Oncology, Vol. 28, No. 23, 10.08.2010, p. 3770-3778.

Research output: Contribution to journalArticle

Climent, J, Perez-Losada, J, Quigley, DA, Kim, IJ, Delrosario, R, Jen, K-Y, Bosch, A, Lluch, A, Mao, JH & Balmain, A 2010, 'Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer', Journal of Clinical Oncology, vol. 28, no. 23, pp. 3770-3778. https://doi.org/10.1200/JCO.2009.27.0215
Climent, Joan ; Perez-Losada, Jesus ; Quigley, David A. ; Kim, Il Jin ; Delrosario, Reyno ; Jen, Kuang-Yu ; Bosch, Ana ; Lluch, Ana ; Mao, Jian Hua ; Balmain, Allan. / Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 23. pp. 3770-3778.
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