Variable alterations of mitochondrial microsatellite instability and DNA copy number in pulmonary hamartomas

AbstractEarly life stress (ELS) has been shown to have a significant impact on typical brain development and the manifestation of psychological disorders through epigenetic modifications that alter gene expression. Line1, a retrotransposon associated with genetic diversity, has been linked with various psychological disorders that are associated with ELS. Our previous work demonstrated altered Line1 DNA copy number in the neonatal period following stressful experiences; we therefore chose to investigate whether early life stress altered Line1 retrotransposition persists into the juvenile period of development. Our study uses a neonatal predator odor exposure (POE) paradigm to model ELS in rats. We examined Line1 using qPCR to assess Line1 expression levels and DNA copy number in the male and female juvenile amygdala, hippocampus and prefrontal cortex—areas chosen for their association with affective disorders and stress. We report a sex difference in Line1 levels within the juvenile amygdala. We also find that ELS significantly increases Line1 DNA copy number within the juvenile amygdala which correlates with reduced juvenile social play levels, suggesting the possibility that Line1 may influence juvenile social development.

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From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis

Medicina ◽

10.3390/medicina57050502 ◽

2021 ◽

Vol 57 (5) ◽

pp. 502

Author(s):

Georgiana Gug ◽

Caius Solovan

Keyword(s):

Mycosis Fungoides ◽

Copy Number ◽

Snp Array ◽

Chromosome 1 ◽

Copy Number Alterations ◽

Dna Copy Number ◽

Large Plaque ◽

Inflammatory Dermatosis ◽

Fresh Frozen ◽

Dna Copy Number Alterations

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

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Elevated mitochondrial DNA copy number found in ubiquinone-deficient clk-1 mutants is not rescued by ubiquinone precursor 2-4-dihydroxybenzoate

Mitochondrion ◽

10.1016/j.mito.2021.02.001 ◽

2021 ◽

Vol 58 ◽

pp. 38-48

Author(s):

Cait S. Kirby ◽

Maulik R. Patel

Keyword(s):

Mitochondrial Dna ◽

Copy Number ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number

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Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation

International Journal of Molecular Sciences ◽

10.3390/ijms22031146 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1146

Author(s):

Reinhard Ullmann ◽

Benjamin Valentin Becker ◽

Simone Rothmiller ◽

Annette Schmidt ◽

Horst Thiermann ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Line ◽

Copy Number ◽

Resistant Cell ◽

Resistant Cell Line ◽

Chromosomal Translocations ◽

Dna Copy Number ◽

Mutational Signatures ◽

Copy Number Changes ◽

And Oxidative Stress

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

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