scholarly journals The QPCR assay for analysis of mitochondrial DNA damage, repair, and relative copy number

Methods ◽  
2010 ◽  
Vol 51 (4) ◽  
pp. 444-451 ◽  
Author(s):  
Senyene E. Hunter ◽  
Dawoon Jung ◽  
Richard T. Di Giulio ◽  
Joel N. Meyer
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Dna Damage Repair ◽  
Qpcr Assay ◽  
Relative Copy Number ◽  
Mitochondrial Dna Damage ◽  
Damage Repair

scholarly journals PCR‐Based Analysis of Mitochondrial DNA Copy Number, Mitochondrial DNA Damage, and Nuclear DNA Damage

2016 ◽  
Vol 67 (1) ◽  
Author(s):  
Claudia P. Gonzalez‐Hunt ◽  
John P. Rooney ◽  
Ian T. Ryde ◽  
Charumathi Anbalagan ◽  
Rashmi Joglekar ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Nuclear Dna ◽  
Dna Copy Number ◽  
Mitochondrial Dna Damage ◽  
Mitochondrial Dna Copy Number

scholarly journals Bioinformatics Analysis the Expression Characteristics of RNA m6A Methylation Regulator in Breast Cancer Progression

2021 ◽  
Author(s):  
Ping Zhao ◽  
Xinwei Huang ◽  
Anhao Wu ◽  
Xin Yang ◽  
Yang Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Protein Binding ◽  
Cancer Progression ◽  
Copy Number ◽  
Dna Damage Repair ◽  
Expression Level ◽  
Copy Number Loss ◽  
Driver Genes ◽  
Damage Repair

Abstract Background: RNA m6A methylation regulator has been shown to play an important regulatory role in tumorigenesis and progression. However, the role and characteristics of RNA m6A methylation in breast cancer are not yet clear. Objective: To analyze the effect of the expression pattern of M6A methylation factor on the progression of breast cancer by bioinformatics.Results: This study uses bioinformatics to analyze three data sets of TCGA-BRCA, GSE96058 and GSE25066. According to the expression level of m6A-related genes, breast cancer samples are divided into 4 subtypes: quiescent, m6A-methylation, protein-binding, and mixed. The results of R-survival analysis showed that the survival of breast cancer samples of the four subtypes was significantly different. The analysis of breast cancer gene expression features showed that there are significant differences in the number of exon skip among the four subtypes. For tumor driver genes, the degree of TP53 mutation and copy number loss are the most in the protein-binding subtype. Among DNA damage repair genes, the copy number of RAD54B in the protein binding subtype is significantly increased, while other DNA damage repair-related genes have fewer mutations and copy number deletions are common. The effect of m6A methylation on the proportion of infiltrated immune cells indicates that Macrophages M0 and Mast cells resting are significantly different in the four m6A subgroups, and are related to patient prognosis. The number of sensitive samples of chemotherapeutics (taxane anthracyclines) is the lowest in the quiescent subtype. In addition, the highest tumor stemness index in breast cancer samples is the protein-bound type, and the lowest is the m6A methylated type. Conclusion: The results of our analysis suggest that the reduced expression level of m6A methylation writer gene and the high expression of m6A reader protein in the four methylation subtypes of breast cancer are key to the progression of breast cancer.

scholarly journals Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer

Theranostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 3939-3951 ◽  
Author(s):  
Zhiyuan Wu ◽  
Sihan Li ◽  
Xuemei Tang ◽  
Yue Wang ◽  
Weiwei Guo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Copy Number ◽  
Dna Damage Repair ◽  
Therapeutic Resistance ◽  
Damage Repair ◽  
Repair Pathways ◽  
Copy Number Amplification

scholarly journals Quantification of mitochondrial DNA damage and copy number in circulating blood of patients with systemic sclerosis by a qPCR-based assay

2020 ◽  
Vol 95 (3) ◽  
pp. 314-319
Author(s):  
Shafieh Movassaghi ◽  
Sara Jafari ◽  
Kowsar Falahati ◽  
Mitra Ataei ◽  
Mohammad Hossein Sanati ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Systemic Sclerosis ◽  
Copy Number ◽  
Mitochondrial Dna Damage

scholarly journals Alterations of BRCA1 and PALB2 Define a Novel Class of Complex-Karyotype AML with a Very Bad Prognosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1677-1677
Author(s):  
Antonella Padella ◽  
Giorgia Simonetti ◽  
Marco Manfrini ◽  
Maria Chiara Fontana ◽  
Giovanni Marconi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Copy Number ◽  
Dna Damage Repair ◽  
Snp Array ◽  
Copy Number Variations ◽  
Chromosome 17 ◽  
Rank Test ◽  
Complex Karyotype ◽  
Damage Repair

Abstract BRCA1 is one of the most important gene associated with familial breast and ovarian cancer susceptibility and is involved in the DNA damage repair and cell cycle arrest. Alterations in BRCA1 and their consequences are well characterized in breast and ovarian tumors, while little is known about its role in Acute Myeloid Leukemia (AML). We aimed to investigate the frequency and the interplay of BRCA1 alterations and patterns of somatic mutations (SNVs) and copy number variations (CNVs) of in AML patients. We genotyped 118 AML samples at either diagnosis or relapse by Single Nucleotide Polymorphism (SNP) array (SNP6.0 and Cytoscan HD, Affymetrix) to detect CNVs. In addition, we performed Whole-Exome Sequencing (WES, 100 bp paired-end, Illumina) of 56 genotyped AML patients to detect SNVs and small indels (MuTect and Varscan 2.0). Differences in survival were assessed using Kaplan-Meier survival analysis and Long-Rank test, or Breslow when indicated. We detected BRCA1 loss in 14 out of 118 patients (12%), ranging from 1,6 Kb to the loss of the entire chromosome 17, with none of the BRCA1 loss patients having a normal karyotype. Moreover, BRCA1 losses significantly co-occurred with PALB2 and RAD50 losses. Notably, the PALB2 loss (chromosome 16) mostly involved exon 12 and was detected also in patients without the BRCA1 loss, with a frequency of 11 out of 118 cases (9%), suggesting a pivotal and previously undescribed role in AML pathogenesis. BRCA1 loss patients were enriched for copy number alterations in genes involved in the regulation of mitotic recombination, DNA repair and positive regulation of kinase activity compared with BRCA1 wild-type cases (p <0.01). To investigate which genes and biological functions cooperates with the pathways affected by structural alterations, we integrated the analysis with WES data on 56 out of 118 AML patients. We focused on the genes involved in the DNA damage repair (DDR) and we identified somatic SNVs in BRCA1, TP53 and in the Fanconi Anemia genes BRCA2 and FANCE. Analysis of co-occurrence and mutual exclusivity revealed that BRCA1 loss and DDR-related alterations (BRCA1, PALB2, BRCA2, and FANCE) were significantly associated with TP53 alterations (p=0.0001 and p=0.0003, respectively). In addition, alterations in the DDR genes were mutually exclusive with mutations in KRAS, IDH1/2, BCOR, BCORL1, NPM1 and myeloid transcription factors as RUNX1 and CEBPA. Notably, patients without alteration in the DDR genes were enriched for mutations in DNMT3A and FLT3. Finally, BRCA1 and PALB2 alterations defined group of patients with poor overall survival (OS). In particular, patients with alterations of either BRCA1 or PALB2 had a worst prognosis compared to patients without alterations in the two genes (p=0.009 and p=0.001, respectively). Patients harboring PALB2 loss had a poorer prognosis compared with patients with complex karyotype (p=0.021, Breslow test). In addition, double BRCA1 and PALB2 loss, single BRAC1 or PALB2 hits and lack of alterations in BRCA1 and PALB2 defined three different classes of risks in our AML cohort (p<0.001). In summary, we define for the first time a novel subgroup of AML patients characterized by alterations targeting the DDR pathway, and in particular the BRCA1 and PALB2 genes. Our data suggest that a signature of genes involved in the DDR and cell cycle regulation synergize and led to the uncontrolled proliferation, independently of DNA damage accumulation. Our results may help improve patient stratification and define ad hoc therapeutic strategies for this aggressive leukemia type. Acknowledgments: ELN, AIL, AIRC, progetto Regione-Università 2010-12 (L. Bolondi), Fondazione del Monte di Bologna e Ravenna, FP7 NGS-PTL project. Disclosures Guadagnuolo: CellPly S.r.l.: Employment. Martinelli:Novartis: Speakers Bureau; Genentech: Consultancy; Roche: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; MSD: Consultancy; Pfizer: Consultancy, Speakers Bureau; Ariad: Consultancy, Speakers Bureau.

scholarly journals Bioinformatics Analysis the Characteristics and Correlation of m6A Methylation in Breast Cancer Progression

2021 ◽  
Author(s):  
Ping Zhao ◽  
Xinwei Huang ◽  
Anhao Wu ◽  
Xin Yang ◽  
Yang Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Protein Binding ◽  
Cancer Progression ◽  
Copy Number ◽  
Dna Damage Repair ◽  
Expression Level ◽  
Copy Number Loss ◽  
Driver Genes ◽  
Damage Repair

Abstract Background: RNA m6A methylation regulator has been shown to play an important regulatory role in tumorigenesis and progression. However, the role and characteristics of RNA m6A methylation in breast cancer are not yet clear. Objective: To analyze the effect of the expression pattern of M6A methylation factor on the progression of breast cancer by bioinformatics.Results: This study uses bioinformatics to analyze three data sets of TCGA-BRCA, GSE96058 and GSE25066. According to the expression level of m6A-related genes, breast cancer samples are divided into 4 subtypes: quiescent, m6A-methylation, protein-binding, and mixed. The results of R-survival analysis showed that the survival of breast cancer samples of the four subtypes was significantly different. The analysis of breast cancer gene expression features showed that there are significant differences in the number of exon skip among the four subtypes. For tumor driver genes, the degree of TP53 mutation and copy number loss are the most in the protein-binding subtype. Among DNA damage repair genes, the copy number of RAD54B in the protein binding subtype is significantly increased, while other DNA damage repair-related genes have fewer mutations and copy number deletions are common. The effect of m6A methylation on the proportion of infiltrated immune cells indicates that Macrophages M0 and Mast cells resting are significantly different in the four m6A subgroups, and are related to patient prognosis. The number of sensitive samples of chemotherapeutics (taxane anthracyclines) is the lowest in the quiescent subtype. In addition, the highest tumor stemness index in breast cancer samples is the protein-bound type, and the lowest is the m6A methylated type. Conclusion: The results of our analysis suggest that the reduced expression level of m6A methylation writer gene and the high expression of m6A reader protein in the four methylation subtypes of breast cancer are key to the progression of breast cancer.

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