Genetic alterations of CCND1 and EMSY in breast cancers

Aims:  CCND1 and EMSY, on 11q13, are frequently amplified in breast cancer. CCND1 is implicated in cell cycle progression and EMSY is a BRCA2‐associated repressor protein. The aim was to investigate gene copy numbers of CCND1 and EMSY and to determine if CCND1 amplification is associated with reduce...

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Published in:Histopathology 2008-05, Vol.52 (6), p.698-705
Main Authors: Kirkegaard, T, Nielsen, K V, Jensen, L B, Campbell, F M, Müller, S, Tovey, S M, Brown, S, Cooke, T G, Bartlett, J M S
Format: Article
Language:English
Subjects:
Biological and medical sciences
breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
CCND1
Cohort Studies
Cyclin D
Cyclins - genetics
EMSY
Female
FISH
Gene Dosage
Gynecology. Andrology. Obstetrics
Humans
Investigative techniques, diagnostic techniques (general aspects)
Mammary gland diseases
Medical sciences
Middle Aged
Neoplasm Proteins - genetics
Nuclear Proteins - genetics
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Repressor Proteins - genetics
Tamoxifen - pharmacology
Tumors
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Summary:Aims:  CCND1 and EMSY, on 11q13, are frequently amplified in breast cancer. CCND1 is implicated in cell cycle progression and EMSY is a BRCA2‐associated repressor protein. The aim was to investigate gene copy numbers of CCND1 and EMSY and to determine if CCND1 amplification is associated with reduced survival of tamoxifen‐treated breast cancer patients. Methods and results:  Fluorescence in situ hybridization (FISH) was performed on 111 consecutive and 354 oestrogen receptor (ER)+ tamoxifen‐treated breast cancers. In the consecutive set, CCND1 and EMSY were amplified in 14.8% and 7.2%, respectively, and deleted in 8.7% and 13.5%, respectively. In the ER+ set, CCND1 and EMSY were amplified in 20.6% and 9.6%, respectively, and deleted in 1.7% and 4.2%, respectively. CCND1 and EMSY gene amplifications were associated with decreased overall survival (OS) (P = 0.03 and P = 0.04, respectively) of patients in the ER+ set. Conclusion:  As hypothesized, CCND1 amplifications are associated with poor OS in ER+ patients. EMSY amplification is also associated with poor OS. However, as >70% of EMSY amplifications were CCND1 amplified, EMSY may not have any additional effect on survival of ER+ breast cancer.
ISSN:0309-0167
1365-2559
DOI:10.1111/j.1365-2559.2008.03007.x