Article
Telomere DNA content predicts breast cancer-free survival interval.
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-0001, USA.
Clinical Cancer Research (impact factor:
7.74).
12/2007;
13(23):7037-43.
DOI:10.1158/1078-0432.CCR-07-0432
Source: PubMed
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Citations (0)
- Cited In (4)
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Article: Prognostic Significance of Telomere Attrition in Ductal Carcinoma in situ of the Breast
[show abstract] [hide abstract]
ABSTRACT: We are using an innovative, quantitative assay for telomere DNA content (TC) developed and characterized by the PI, to test the hypothesis that TC predicts the likelihood of disease recurrence in women with ductal carcinoma in situ (DCIS). In Year One, we collaborated to determine whether TC measured in bulk DCIS tumor tissue is comparable to that measured in tumor epithelial cells purified by laser-capture microscopy. In 7/10 instances, TC in microdissected specimens was 72-112% of that in the undissected control. In Years Two and Three, we confirmed and extended these results in our own laboratory. TC in microdissected samples was compared to TC in unfractionated samples; in 10/10 instances, TC in the microdissected sample was 75-124% of that in the undissected (i.e. bulk) control. These results confirm that it is not necessary to microdissect DCIS specimens prior to TC analysis. In Years One-Three, we measured TC in 75 normal breast, 126 DCIS and 657 breast tumor specimens. In Year Two, we used a Kaplan-Meier plot and log-rank test to show that low TC predicts a shorter survival interval. TC was not associated with ethnicity, menopausal status, or the expression of several other markers, including ER, PR, p53, Ki67, and Her2. In Years Three-Four, we demonstrated an association between TC, the extent of allelic imbalance and tumor stage. In Year Four, we obtained longer follow-up to confirm and extend these results. In summary, we have shown that (i) meaningful TC measurements can be obtained with bulk DCIS tissues, (ii) TC is associated with tumor stage and (iii) TC in DCIS is associated with breast cancer-free survival.01/2009; -
Article: Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells.
[show abstract] [hide abstract]
ABSTRACT: Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.Nucleic Acids Research 12/2011; 40(6):2554-65. · 8.03 Impact Factor -
Article: Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells
[show abstract] [hide abstract]
ABSTRACT: Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.Nucleic Acids Research 01/2011; · 8.03 Impact Factor
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Keywords
12 risk factors
adjusted relative hazard
adjuvant therapy
breast tumor tissues
chemotherapy sequence
conferred significant relative hazards
estrogen receptor
estrogen receptor status
Fisher's exact test
high-TC group
independent predictor
multivariate Cox proportional hazards models
new primary breast tumor
p53 status
progesterone receptor
protect chromosome
quantitate TC
telomere DNA content
telomere DNA loss
tumor-node-metastasis stage
