High CCND1 amplification (CNG > or = 8) may identify a subset of patients with poor prognosis ER-positive breast cancers who should be considered for additional therapy.
These results suggest that the frequency of overexpression is much higher than previously concluded from DNA-based analyses and that more than one-third of human breast cancers may contain excessive levels of cyclin D1.
We show that there are clusters of genophenotypic abnormalities that distinguish lobular breast cancers from nonlobular tumors; that cyclin D1 amplification occurs prior to the divergence of lobular breast cancers from nonlobular cancers; that p53 dysfunction, Her-2/neu amplification, and c-myc amplification are characteristic features of nonlobular breast cancers, but not of lobular breast cancers; and that the frequencies of amplification of all three oncogenes examined increase progressively with increasing aneuploidy, but that each gene exhibits a different profile of increasing amplification in relation to tumor progression.
Collectively, the results of this study suggest that only the combined inhibition of Cyclin D1 and D3 might be a suitable strategy for breast cancer prevention and therapy.
These results strongly suggest that daintain/AIF-1 can promote the growth of breast tumors via activating NF-kappaB signaling, which consequently up-regulates the expression of cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the prognosis and therapy of breast cancer.
On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively).
Cyclin D1 and cyclin E are overexpressed in approximately 45% and 30% of breast cancers, respectively, and adverse associations with patient outcome have been reported.
These data suggest that cyclin D1 may be a target gene for PRL in normal lobuloalveolar development, as well as in the development and/or progression of mammary cancer.
The variations of CCND1, Rb1, and CHEK2 were significantly correlated with poor survival in the young breast cancer patient group, while the amplification of c-Myc was not obviously correlated with poor survival in young breast cancer patients.
Compared to female breast cancers, EGFR (p = 0.005) and CCND1 (p = 0.041) copy number gain was more often seen in male breast cancer, while copy number gain of EMSY (p = 0.004) and CPD (p = 0.001) and amplification in general was less frequent.
We concluded CCND1G870A polymorphism make significant contribution to breast cancer in the country with the preponderance of breast cancer in young women.
In this study, we analyzed 3 polymorphisms E2F2_-5368_A>G, CCND1_870_A>G and CCND3_-677_C>T located in genes involved in cell cycle regulation in the GENICA population-based and age-matched breast cancer case-control study from Germany.
PRAD1 (previously D11S287) is a putative proto-oncogene at 11q13, activated by overexpression through gene rearrangement or gene amplification in several types of human tumors including parathyroid adenomas, centrocytic lymphomas and other B-cell tumors with t(11;14), and breast cancers.
The relationship between cyclin D1 amplification and clinicopathological parameters in patients with breast cancer remains controversial and its impact on survival outcome is not completely clear.
The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR=0.67, 95% CI 0.45-0.99) when compared with the GG genotype.
The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines.
To demonstrate the reliability of the probes generated with this protocol, four strategies were employed: (i) probes mapping to cyclin D1 (CCND1) were generated and their performance was compared with that of a commercially available probe for the same gene in a series of 10 FFPETS of breast cancer samples of which five harboured CCND1 amplification; (ii) probes targeting cyclin-dependent kinase 4 were used to validate an amplification identified by microarray-based comparative genomic hybridization (aCGH) in a pleomorphic adenoma; (iii) probes targeting fibroblast growth factor receptor 1 and CCND1 were used to validate amplifications mapping to these regions, as defined by aCGH, in an invasive lobular breast carcinoma with FISH and CISH; and (iv) gene-specific probes for ETV6 and NTRK3 were used to demonstrate the presence of t(12;15)(p12;q25) translocation in a case of breast secretory carcinoma with dual colour FISH.