Molecular Basis of Genomic Instability in Breast Cancer: Regulation of the Centrosome Duplication Cycle

2003 ◽  
Author(s):  
Jian Du ◽  
Gregory Hannon
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Molecular Basis ◽  
Centrosome Duplication ◽  
Duplication Cycle

scholarly journals Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1331
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Olga Savichtcheva ◽  
Kimberly A. Holden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genomic Instability ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
T1 And T2 ◽  
Tumor Dna

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

scholarly journals Genomic instability-derived plasma extracellular vesicle-microRNA signature as a minimally invasive predictor of risk and unfavorable prognosis in breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Siqi Bao ◽  
Ting Hu ◽  
Jiaqi Liu ◽  
Jianzhong Su ◽  
Jie Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Minimally Invasive ◽  
Genomic Instability ◽  
Extracellular Vesicles ◽  
Disease Risk ◽  
Prognostic Indicator ◽  
Mirna Regulation ◽  
Mirna Signature ◽  
Operating Characteristics

Abstract Background Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-associated deaths in women. Recent studies have indicated that microRNA (miRNA) regulation in genomic instability (GI) is associated with disease risk and clinical outcome. Herein, we aimed to identify the GI-derived miRNA signature in extracellular vesicles (EVs) as a minimally invasive biomarker for early diagnosis and prognostic risk stratification. Experimental design Integrative analysis of miRNA expression and somatic mutation profiles was performed to identify GI-associated miRNAs. Then, we constructed a discovery and validation study with multicenter prospective cohorts. The GI-derived miRNA signature (miGISig) was developed in the TCGA discovery cohort (n = 261), and was subsequently independently validated in internal TCGA validation (n = 261) and GSE22220 (n = 210) cohorts for prognosis prediction, and in GSE73002 (n = 3966), GSE41922 (n = 54), and in-house clinical exosome (n = 30) cohorts for diagnostic performance. Results We identified a GI-derived three miRNA signature (MIR421, MIR128-1 and MIR128-2) in the serum extracellular vesicles of BC patients, which was significantly associated with poor prognosis in all the cohorts tested and remained as an independent prognostic factor using multivariate analyses. When integrated with the clinical characteristics, the composite miRNA-clinical prognostic indicator showed improved prognostic performance. The miGISig also showed high accuracy in differentiating BC from healthy controls with the area under the receiver operating characteristics curve (ROC) with 0.915, 0.794 and 0.772 in GSE73002, GSE41922 and TCGA cohorts, respectively. Furthermore, circulating EVs from BC patients in the in-house cohort harbored elevated levels of miGISig, with effective diagnostic accuracy. Conclusions We report a novel GI-derived three miRNA signature in EVs, as an excellent minimally invasive biomarker for the early diagnosis and unfavorable prognosis in BC.

The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model

2007 ◽  
Vol 616 (1-2) ◽  
pp. 201-209 ◽  
Author(s):  
El Mustapha Bahassi ◽  
C. Gail Penner ◽  
Susan B. Robbins ◽  
Elisia Tichy ◽  
Estrella Feliciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Genomic Instability ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Susceptibility Allele ◽  
Chek2 1100Delc

scholarly journals Breast cancer risk among Swedish hemangioma patients and possible consequences of radiation-induced genomic instability

2009 ◽  
Vol 669 (1-2) ◽  
pp. 48-55 ◽  
Author(s):  
Markus Eidemüller ◽  
Erik Holmberg ◽  
Peter Jacob ◽  
Marie Lundell ◽  
Per Karlsson
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genomic Instability ◽  
Radiation Induced

scholarly journals Estimating genomic instability mediated by Alu retroelements in breast cancer

2009 ◽  
Vol 32 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Ana Cristina Fazza ◽  
Flavia Cal Sabino ◽  
Nathalia de Setta ◽  
Newton Antonio Bordin Jr. ◽  
Eloiza Helena Tajara da Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genomic Instability

Effect of Diets, Familial History, and Alternative Therapies on Genomic Instability of Breast Cancer Patients

2018 ◽  
Vol 188 (1) ◽  
pp. 282-296
Author(s):  
Márcia Fernanda Correia Jardim Paz ◽  
Antônio Luiz Gomes Júnior ◽  
Marcus Vinícius Oliveira Barros de Alencar ◽  
Shams Tabrez ◽  
Muhammad Torequl Islam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Genomic Instability ◽  
Alternative Therapies ◽  
Breast Cancer Patients ◽  
Familial History
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