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 language | English (US) |
|---|---|
| Pages (from-to) | 3770-3778 |
| Number of pages | 9 |
| Journal | Journal of Clinical Oncology |
| Volume | 28 |
| Issue number | 23 |
| DOIs | |
| State | Published - Aug 10 2010 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
TY - JOUR
T1 - Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer
AU - Climent, Joan
AU - Perez-Losada, Jesus
AU - Quigley, David A.
AU - Kim, Il Jin
AU - Delrosario, Reyno
AU - Jen, Kuang-Yu
AU - Bosch, Ana
AU - Lluch, Ana
AU - Mao, Jian Hua
AU - Balmain, Allan
PY - 2010/8/10
Y1 - 2010/8/10
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77957268473&partnerID=8YFLogxK
U2 - 10.1200/JCO.2009.27.0215
DO - 10.1200/JCO.2009.27.0215
M3 - Article
C2 - 20625127
AN - SCOPUS:77957268473
VL - 28
SP - 3770
EP - 3778
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 23
ER -