Prognostic value of CCND1 gene status in sporadic breast tumours, as determined by real-time quantitative PCR assays

The CCND1 gene, a key cell-cycle regulator, is often altered in breast cancer, but the mechanisms underlying CCND1 dysregulation and the clinical significance of CCND1 status are unclear. We used real-time quantitative PCR and RT-PCR assays based on fluorescent TaqMan methodology to quantify CCND1 g...

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Bibliographic Details
Published in:British journal of cancer 2002-02, Vol.86 (4), p.580-586
Main Authors: Bièche, I, Olivi, M, Noguès, C, Vidaud, M, Lidereau, R
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cyclin D1 - genetics
Cyclin D1 - metabolism
DNA Primers - chemistry
DNA, Neoplasm - analysis
Female
Genes, erbB-2 - genetics
Genes, myc - genetics
Genetics and Genomics
Humans
Middle Aged
Prognosis
Receptors, Estrogen - analysis
Reference Values
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
RNA, Neoplasm - metabolism
Survival Rate
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Summary:The CCND1 gene, a key cell-cycle regulator, is often altered in breast cancer, but the mechanisms underlying CCND1 dysregulation and the clinical significance of CCND1 status are unclear. We used real-time quantitative PCR and RT-PCR assays based on fluorescent TaqMan methodology to quantify CCND1 gene amplification and expression in a large series of breast tumours. CCND1 overexpression was observed in 44 (32.8%) of 134 breast tumour RNAs, ranging from 3.3 to 43.7 times the level in normal breast tissues, and correlated significantly with positive oestrogen receptor status (P=0.0003). CCND1 overexpression requires oestrogen receptor integrity and is exacerbated by amplification at 11q13 (the site of the CCND1 gene), owing to an additional gene dosage effect. Our results challenge CCND1 gene as the main 11q13 amplicon selector. The relapse-free survival time of patients with CCND1-amplified tumours was shorter than that of patients without CCND1 alterations, while that of patients with CCND1-unamplified-overexpressed tumours was longer (P=0.011). Only the good prognostic significance of CCND1-unamplified-overexpression status persisted in Cox multivariate regression analysis. This study confirms that CCND1 is an ER-responsive or ER-coactivator gene in breast cancer, and points to the CCND1 gene as a putative molecular marker predictive of hormone responsiveness in breast cancer. Moreover, CCND1 amplification status dichotomizes the CCND1-overexpressing tumors into two groups with opposite outcomes.
ISSN:0007-0920
1532-1827
DOI:10.1038/sj.bjc.6600109