The Interplay Between Estrogen and Replication Origins in Breast Cancer DNA Amplification

2012 ◽  
Author(s):  
Cinzia Casella
2021 ◽  
Vol 11 ◽  
Author(s):  
Peide Huang ◽  
Fengyu Li ◽  
Zongchao Mo ◽  
Chunyu Geng ◽  
Fang Wen ◽  
...  

To investigate the relationship between non-coding RNAs [especially circular RNAs (circRNAs)] and docetaxel resistance in breast cancer, and to find potential predictive biomarkers for taxane-containing therapies, we have performed transcriptome and microRNA (miRNA) sequencing for two established docetaxel-resistant breast cancer (DRBC) cell lines and their docetaxel-sensitive parental cell lines. Our analyses revealed differences between circRNA signatures in the docetaxel-resistant and -sensitive breast cancer cells, and discovered circRNAs generated by multidrug-resistance genes in taxane-resistant cancer cells. In DRBC cells, circABCB1 was identified and validated as a circRNA that is strongly up-regulated, whereas circEPHA3.1 and circEPHA3.2 are strongly down-regulated. Furthermore, we investigated the potential functions of these circRNAs by bioinformatics analysis, and miRNA analysis was performed to uncover potential interactions between circRNAs and miRNAs. Our data showed that circABCB1, circEPHA3.1 and circEPHA3.2 may sponge up eight significantly differentially expressed miRNAs that are associated with chemotherapy and contribute to docetaxel resistance via the PI3K-Akt and AGE-RAGE signaling pathways. We also integrated differential expression data of mRNA, long non-coding RNA, circRNA, and miRNA to gain a global profile of multi-level RNA changes in DRBC cells, and compared them with changes in DNA copy numbers in the same cell lines. We found that Chromosome 7 q21.12-q21.2 was a common region dominated by multi-level RNA overexpression and DNA amplification, indicating that overexpression of the RNA molecules transcribed from this region may result from DNA amplification during stepwise exposure to docetaxel. These findings may help to further our understanding of the mechanisms underlying docetaxel resistance in breast cancer.


2019 ◽  
Vol 10 (1) ◽  
pp. 120-127
Author(s):  
Tani Sagna ◽  
Elena Bonora ◽  
Marie Nabonswindé Lamoussa Ouedraogo ◽  
Daniela Fusco ◽  
Abdou Azaque Zoure ◽  
...  

AbstractBreast cancer is the top cause of cancer mortality among women in the world and the second in Africa. The aims of this study were to: i) identify women with breast nodules suspected of having breast cancer ii) sequence the BRCA1 and BRCA2 genes and iii) screen mutations. From 2015 to 2016, 112 women aged from 35 to 44 years, who had come for consultation in the gynecology/obstetrics and the oncology department of the University Hospital Yalgado Ouedraogo, voluntarily agreed to participate to this study. Whole blood was collected from those with mammary nodules. The genomic DNA was extracted using Qiagen kit. FAST KAPA was used for genomic DNA amplification and the purified PCR products were analyzed by direct sequencing using Big Dye v1.1 and ABI 3730 automated sequencer. Nucleotides substitutions were determined. We identified BRCA1 SNPs rs1799966, rs799917, rs16942, rs16941, rs2227945, and BRCA2 SNPs rs169547, rs4986860. These identified variants are found mostly in cases of benign tumors of breast or ovarian cancer with familial history of breast cancer. This study in Burkina-Faso, is the basis for improved and more specific genetic testing, and suggests that additional genes contributing to an increased risk of breast cancer should be analyzed.


2002 ◽  
Vol 102 (6) ◽  
pp. 608-614 ◽  
Author(s):  
Johannes W.G. Janssen ◽  
Marguerite Cuny ◽  
Béatrice Orsetti ◽  
Carmen Rodriguez ◽  
Hélène Vallés ◽  
...  

2019 ◽  
Vol 21 (1) ◽  
pp. 217 ◽  
Author(s):  
Eriko Katsuta ◽  
Li Yan ◽  
Takashi Takeshita ◽  
Kerry-Ann McDonald ◽  
Subhamoy Dasgupta ◽  
...  

DNA abnormalities are used in inclusion criteria of clinical trials for treatments with specific targeted molecules. MYC is one of the most powerful oncogenes and is known to be associated with triple-negative breast cancer (TNBC). Its DNA amplification is often part of the targeted DNA-sequencing panels under the assumption of reflecting upregulated signaling. However, it remains unclear if MYC DNA amplification is a surrogate of its upregulated signaling. Thus, we investigated the difference between MYC DNA amplification and mRNA high expression in TNBCs utilizing publicly available cohorts. MYC DNA amplified tumors were found to have various mRNA expression levels, suggesting that MYC DNA amplification does not always result in elevated MYC mRNA expression. Compared to other subtypes, both MYC DNA amplification and mRNA high expression were more frequent in the TNBCs. MYC mRNA high expression, but not DNA amplification, was significantly associated with worse overall survival in the TNBCs. The TNBCs with MYC mRNA high expression enriched MYC target genes, cell cycle related genes, and WNT/β-catenin gene sets, whereas none of them were enriched in MYC DNA amplified TNBCs. In conclusion, MYC mRNA high expression, but not DNA amplification, reflects not only its upregulated signaling pathway, but also clinical significance in TNBCs.


2010 ◽  
Vol 123 (18) ◽  
pp. 3047-3051 ◽  
Author(s):  
L. Kiang ◽  
C. Heichinger ◽  
S. Watt ◽  
J. Bahler ◽  
P. Nurse

2011 ◽  
Vol 22 (2) ◽  
pp. 232-245 ◽  
Author(s):  
J. Guenthoer ◽  
S. J. Diede ◽  
H. Tanaka ◽  
X. Chai ◽  
L. Hsu ◽  
...  

2006 ◽  
Vol 2006 ◽  
pp. 1-5 ◽  
Author(s):  
Brian H. Crawford ◽  
AKM A. Hussain ◽  
Nathan M. Jideama

This study investigated the use of DNA amplification fingerprinting (DAF) to identify biomarkers useful in the elucidating genetic factors that lead to carcinogenesis. The DNA amplification fingerprinting (DAF) technique was used to generate fingerprint profiles of a normal human mammary epithelial cell line (MCF-10A) and a human breast cancer cell line (MCF-7). When compared with one another, a polymorphic biomarker gene (262base pairs (bps)) was identified in MCF-10A but was not present in MCF-7. This gene was cloned from the genomic DNA of the MCF-10A cell line, and subjected to Genbank database analysis. The analysis of the nucleotide sequence polymorphic marker (Genbank account: AC079630) shows that this biomarker has100%homology with the nucleotide sequence of human chromosome12BAC RP11-476D10(bps19612-19353). The nucleotide sequence was used for possible protein translation product and the result obtained indicated that the gene codes for hypothetical protein XF2620. In order to evaluate the effects that the262bps biomarker would have on the morphology of MCF-7cells, it was transfected into MCF-7cells. There were observable changes in the morphology of the transfected cells. These changes included an increase in cell elongation and a decrease in cell aggregation.


1998 ◽  
Vol 16 (4) ◽  
pp. 1340-1349 ◽  
Author(s):  
I L Andrulis ◽  
S B Bull ◽  
M E Blackstein ◽  
D Sutherland ◽  
C Mak ◽  
...  

PURPOSE It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.


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