scholarly journals Mitochondrial DNA Copy Number Variation as a Potential Predictor of Renal Cell Carcinoma

2017 ◽  
Vol 32 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Eman T. Elsayed ◽  
Mohamed M. Hashad ◽  
Iman E. Elgohary
Keyword(s):  
Renal Cell Carcinoma ◽  
Mitochondrial Dna ◽  
Copy Number Variation ◽  
Peripheral Blood ◽  
Predictive Value ◽  
Renal Cell ◽  
Copy Number ◽  
Mtdna Copy Number ◽  
Increased Risk ◽  
Number Variation

Background Peripheral blood mitochondrial DNA (mtDNA) copy number alteration has been suggested as a risk factor for several types of cancer. The aim of the present study was to assess the role of peripheral blood mtDNA copy number variation as a noninvasive biomarker in the prediction and early detection of renal cell carcinoma (RCC) in a cohort of Egyptian patients. Methods Quantitative real-time polymerase chain reaction (qPCR) was used to measure peripheral blood mtDNA copy numbers in 57 patients with newly diagnosed, early-stage localized RCC and 60 age- and sex-matched healthy individuals as a control group. Results Median mtDNA copy number was significantly higher in RCC cases than in controls (166 vs. 91, p<0.001). Increased mtDNA copy number was associated with an 18-fold increased risk of RCC (95% confidence interval: 5.065-63.9). On receiver operating characteristic curve analysis, it was found that mtDNA could distinguish between RCC patients and healthy controls, with 86% sensitivity, 80% specificity, 80.3% positive predictive value and 85.7% negative predictive value at a cutoff value of 108.5. Conclusions Our results showed that increased peripheral blood mtDNA copy number was associated with increased risk of RCC. Therefore, RCC might be considered as part of a range of potential tumors in cases with elevated blood mtDNA copy number.

scholarly journals A Case-Control Study of Peripheral Blood Mitochondrial DNA Copy Number and Risk of Renal Cell Carcinoma

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43149 ◽  
Author(s):  
Mark P. Purdue ◽  
Jonathan N. Hofmann ◽  
Joanne S. Colt ◽  
Mirjam Hoxha ◽  
Julie J. Ruterbusch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Mitochondrial Dna ◽  
Cell Carcinoma ◽  
Peripheral Blood ◽  
Renal Cell ◽  
Copy Number ◽  
Case Control Study ◽  
Case Control ◽  
Mitochondrial Dna Copy Number ◽  
Control Study

scholarly journals Mitochondrial DNA Copy Number Variation Across Human Cancers

2015 ◽  
Author(s):  
Ed Reznik ◽  
Martin Miller ◽  
Yasin Senbabaoglu ◽  
Nadeem Riaz ◽  
William Lee ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number Variation ◽  
Copy Number ◽  
Large Scale ◽  
Tumor Type ◽  
Mtdna Copy Number ◽  
Tissue Samples ◽  
Mitochondrial Dna Copy Number ◽  
Number Variation ◽  
Tumor Types

In cancer, mitochondrial dysfunction, through mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), contributes to the malignant transformation and progression of tumors. Here, we report the first large-scale survey of mtDNA copy number variation across 21 distinct solid tumor types, examining over 13,000 tissue samples profiled with next-generation sequencing methods. We find a tendency for cancers, especially of the bladder and kidney, to be significantly depleted of mtDNA, relative to matched normal tissue. We show that mtDNA copy number is correlated to the expression of mitochondrially-localized metabolic pathways, suggesting that mtDNA copy number variation reflect gross changes in mitochondrial metabolic activity. Finally, we identify a subset of tumor-type-specific somatic alterations, including IDH1 and NF1 mutations in gliomas, whose incidence is strongly correlated to mtDNA copy number. Our findings suggest that modulation of mtDNA copy number may play a role in the pathology of cancer.

scholarly journals Mitochondrial DNA copy number variation across human cancers

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Ed Reznik ◽  
Martin L Miller ◽  
Yasin Şenbabaoğlu ◽  
Nadeem Riaz ◽  
Judy Sarungbam ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number Variation ◽  
Copy Number ◽  
The Cancer Genome Atlas ◽  
Mtdna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
Number Variation ◽  
Somatic Alterations ◽  
Immunohistochemical Evidence ◽  
Tumor Types

Mutations, deletions, and changes in copy number of mitochondrial DNA (mtDNA), are observed throughout cancers. Here, we survey mtDNA copy number variation across 22 tumor types profiled by The Cancer Genome Atlas project. We observe a tendency for some cancers, especially of the bladder, breast, and kidney, to be depleted of mtDNA, relative to matched normal tissue. Analysis of genetic context reveals an association between incidence of several somatic alterations, including IDH1 mutations in gliomas, and mtDNA content. In some but not all cancer types, mtDNA content is correlated with the expression of respiratory genes, and anti-correlated to the expression of immune response and cell-cycle genes. In tandem with immunohistochemical evidence, we find that some tumors may compensate for mtDNA depletion to sustain levels of respiratory proteins. Our results highlight the extent of mtDNA copy number variation in tumors and point to related therapeutic opportunities.

Impact of chromosomal copy number variation on outcome in metastatic clear cell renal cell carcinoma patients treated with antiangiogenic agents.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 393-393
Author(s):  
Eric Jonasch ◽  
Suresh Thakur ◽  
Kanishka Sircar ◽  
Pheroze Tamboli ◽  
Nizar M. Tannir ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Copy Number Variation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Copy Number ◽  
Clear Cell ◽  
Response To Therapy ◽  
Antiangiogenic Agents ◽  
Cell Renal Cell Carcinoma ◽  
Number Variation

393 Background: Antiangiogenic agents (AA) are used to treat metastatic clear cell renal cell carcinoma (ccRCC). Currently there are no biomarkers of therapeutic efficacy with these agents. We have previously shown that chromosome copy number variation (CNV) is associated with poor (14q loss) or more favorable outcomes (5q31-ter gain) in nonmetastatic patients. The purpose of the current study was the impact of CNV on response, progression free survival (PFS) and on overall survival (OS) after AA in patients with metastatic ccRCC. Methods: We obtained archival FFPE or frozen tumor specimens from patients with mRCC treated with sorafenib (after tumor removal), bevacizumab or sunitinib (neoadjuvant treatment). DNA was analyzed with Affymetrix 250K Nsp SNP microarrays. We identified the presence of genomic imbalances and loss of heterozygosity (LOH) to obtain “virtual karyotypes”. We then compared CNV to outcome using Wilcoxon-Gehan statistical analysis. Results: A total of 83 patients were used to analyze CNV after treatment with AA: 22 sorafenib, 29 sunitinib, 31 bevacizumab. Gain of 8q (p = 0.036) and loss of 16q (p = 0.0031), 20p (p = 0.038) or 20q (p = 0.022) were associated with a shorter OS, whereas gain of 1q (p = 0.037) and 5q (p = 0.019) were associated with longer OS in this patient cohort. When 14q loss was combined with 8q gain, median OS was further decreased (p 0.01). Surprisingly, when assessed as a group, no specific CNV was associated with PFS. However, when compared separately, 5q gain was predictive for better PFS in sorafenib or bevacizumab treated patients (p = 0.006), but no such effect was seen in the sunitinib treated cohort. Conclusions: Our results show that chromosomal imbalances are associated with divergent clinical outcome in metastatic ccRCC patients treated with AA, and are predominantly prognostic. Dissecting out driver tumor suppressor or tumor activating genes within these chromosomal regions will guide our understanding of what defines a particularly lethal phenotype. The possibility exists that specific CNV profiles predict for response to therapy, but a larger sample size is required to validate this possibility.

scholarly journals A sex chromosome inversion is associated with copy number variation of mitochondrial DNA in zebra finch sperm

2021 ◽  
Vol 8 (9) ◽  
pp. 211025
Author(s):  
Ulrich Knief ◽  
Wolfgang Forstmeier ◽  
Bart Kempenaers ◽  
Jochen B. W. Wolf
Keyword(s):  
Mitochondrial Dna ◽  
Copy Number Variation ◽  
Zebra Finch ◽  
Copy Number ◽  
Sex Chromosome ◽  
Species Variation ◽  
Zebra Finches ◽  
Mtdna Copy Number ◽  
Number Variation ◽  
Sperm Midpiece

The propulsion of sperm cells via movement of the flagellum is of vital importance for successful fertilization. While the exact mechanism of energy production for this movement varies between species, in avian species energy is thought to come predominantly from the mitochondria located in the sperm midpiece. Larger midpieces may contain more mitochondria, which should enhance the energetic capacity and possibly promote mobility. Due to an inversion polymorphism on their sex chromosome TguZ , zebra finches ( Taeniopygia guttata castanotis ) exhibit large within-species variation in sperm midpiece length, and those sperm with the longest midpieces swim the fastest. Here, we test through quantitative real-time PCR in zebra finch ejaculates whether the inversion genotype has an effect on the copy number of mitochondrial DNA (mtDNA). We find that zebra finches carrying the derived allele (correlated with longer sperm midpieces) have more copies of the mtDNA in their ejaculates than those homozygous for the ancestral allele (shorter midpieces). We suggest downstream effects of mtDNA copy number variation on the rate of adenosine triphosphate production, which in turn may influence sperm swimming speed and fertilization success. Central components of gamete energy metabolism may thus be the proximate cause for a fitness-relevant genetic polymorphism, stabilizing a megabase-scale inversion at an intermediate allele frequency in the wild.

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