title: Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer.
abstract: OBJECTIVE
  To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, Cancer Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Climent
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez-Losada
authors.forename: David A
authors.initials: DA
authors.lastname: Quigley
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.forename: Reyno
authors.initials: R
authors.lastname: Delrosario
authors.forename: Kuang-Yu
authors.initials: KY
authors.lastname: Jen
authors.forename: Ana
authors.initials: A
authors.lastname: Bosch
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Mao
authors.forename: Allan
authors.initials: A
authors.lastname: Balmain
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D009364:Neoplasm Recurrence, Local; D056950:Period Circadian Proteins / Q000235:genetics*; D011379:Prognosis; D011960:Receptors, Estrogen; D017384:Sequence Deletion; D016019:Survival Analysis
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins; D011960:Receptors, Estrogen