scholarly journals Focal amplifications are associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xue-Ke Zhao ◽  
Pengwei Xing ◽  
Xin Song ◽  
Miao Zhao ◽  
Linxuan Zhao ◽  
...  
Keyword(s):  
Dna Damage ◽  
Prognostic Marker ◽  
Survival Probability ◽  
Large Scale ◽  
Dietary Habits ◽  
Gastric Cardia ◽  
Gastric Cardia Adenocarcinoma ◽  
Extrachromosomal Dna

AbstractThe role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients.

scholarly journals Extrachromosomal DNA is associated with chromothripsis events and diverse prognoses in gastric cardia adenocarcinoma

2021 ◽  
Author(s):  
Xueke Zhao ◽  
Pengwei Xing ◽  
Xin Song ◽  
Miao Zhao ◽  
Linxuan Zhao ◽  
...  
Keyword(s):  
Large Scale ◽  
Dietary Habits ◽  
Good Prognosis ◽  
Geographic Region ◽  
Gastric Cardia ◽  
Gastric Cardia Adenocarcinoma ◽  
Extrachromosomal Dna ◽  
Chinese Cohort ◽  
Poor Outcomes ◽  
And Function

Extrachromosomal DNA plays an important role in oncogene amplification in tumour cells and poor outcomes across multiple cancers. However, the function of extrachromosomal DNA in gastric cardia adenocarcinoma (GCA) is very limited. Here, we investigated the availability and function of extrachromosomal DNA in GCA from a Chinese cohort of GCA using whole-genome sequencing (WGS), whole-exome sequencing (WES), and immunohistochemistry. For the first time, we identified the ecDNA amplicons present in most GCA patients, and found that some oncogenes are present as ecDNA amplicons in these patients. We found that oncogene ecDNA amplicons in the GCA cohort were associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits in the geographic region. Strikingly, we observed diverse correlations between the presence of ecDNA oncogene amplicons and prognosis, where ERBB2 ecDNA amplicons correlated with good prognosis, EGFR ecDNA amplicons correlated with poor prognosis, and CCNE1 ecDNA amplicons did not correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients revealed that there was a positive correlation between the presence of ERBB2 and prognosis in 2-7-year survival; however, there was a negative correlation between the presence of ERBB2 and prognosis in 0-2-year survival. Our observations indicate that the presence of ERBB2 ecDNA in GCA patients may represent a good prognosis marker.

scholarly journals Mechanisms of replication and repair in mitochondrial DNA deletion formation

2020 ◽  
Vol 48 (20) ◽  
pp. 11244-11258
Author(s):  
Gabriele A Fontana ◽  
Hailey L Gahlon
Keyword(s):  
Dna Damage ◽  
Mitochondrial Dna ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Mitochondrial Dna Deletion ◽  
Deletion Formation ◽  
Dna Deletion ◽  
Mtdna Deletions ◽  
Mtdna Deletion

Abstract Deletions in mitochondrial DNA (mtDNA) are associated with diverse human pathologies including cancer, aging and mitochondrial disorders. Large-scale deletions span kilobases in length and the loss of these associated genes contributes to crippled oxidative phosphorylation and overall decline in mitochondrial fitness. There is not a united view for how mtDNA deletions are generated and the molecular mechanisms underlying this process are poorly understood. This review discusses the role of replication and repair in mtDNA deletion formation as well as nucleic acid motifs such as repeats, secondary structures, and DNA damage associated with deletion formation in the mitochondrial genome. We propose that while erroneous replication and repair can separately contribute to deletion formation, crosstalk between these pathways is also involved in generating deletions.

scholarly journals Budding Yeast CTDK-I Is Required for DNA Damage-Induced Transcription

2003 ◽  
Vol 2 (2) ◽  
pp. 274-283 ◽  
Author(s):  
Denis Ostapenko ◽  
Mark J. Solomon
Keyword(s):  
Dna Damage ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Large Scale ◽  
Large Subunit ◽  
Growth Conditions ◽  
Dna Damaging Agents ◽  
Irradiation Treatment ◽  
Mutant Cells

ABSTRACT CTDK-I phosphorylates the C-terminal domain (CTD) of the large subunit of yeast RNA polymerase II in a reaction that stimulates transcription elongation. Mutations in CTDK-I subunits—Ctk1p, Ctk2p, and Ctk3p—confer conditional phenotypes. In this study, we examined the role of CTDK-I in the DNA damage response. We found that mutation of individual CTDK-I subunits rendered yeast sensitive to hydroxyurea (HU) and UV irradiation. Treatment with DNA-damaging agents increased phosphorylation of Ser2 within the CTD repeats in wild-type but not in ctk1Δ mutant cells. Using microarray hybridization, we identified genes whose transcription following DNA damage is Ctk1p dependent, including several DNA repair and stress response genes. Following HU treatment, the level of Ser2-phosphorylated RNA polymerase II increased both globally and on the CTDK-I-regulated genes. The pleiotropic phenotypes of ctk mutants suggest that CTDK-I activity is essential during large-scale transcriptional repatterning under stress and unfavorable growth conditions.

Critical evaluation of p53 as a prognostic marker in ovarian cancer

2004 ◽  
Vol 6 (12) ◽  
pp. 1-20 ◽  
Author(s):  
Jacqueline Hall ◽  
Jim Paul ◽  
Robert Brown
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Clinical Outcome ◽  
Prognostic Marker ◽  
Clinical Studies ◽  
Critical Evaluation ◽  
Experimental Studies ◽  
Minimum Criteria

The tumour suppressor gene encoding p53 has been shown from experimental studies to have a crucial role in how cells respond to DNA damage. p53 has important functions in apoptosis, cell-cycle arrest and DNA repair, largely mediated by its activity on gene transcription. However, despite this wealth of in vitro data, its role in how tumours respond to DNA damage induced by chemotherapeutic drugs remains controversial. In this review, we highlight some of the problems surrounding design and analysis of studies of p53 as a prognostic marker of clinical outcome, using ovarian cancer as an example. We aim to build on the knowledge of the published literature in ovarian cancer to identify criteria for clinical studies that should give a more definitive estimate of the role of p53 in clinical drug resistance. A search of three public databases using keywords combined with Boolean operators identified 64 clinical publications investigating the relationship of p53 to clinical outcome following chemotherapy in ovarian cancer. Although 43% of 215 published analyses from the 64 papers reported a significant correlation between p53 status and a clinical endpoint relevant to chemoresistance, only six analyses fulfil minimum criteria and none of these finds a statistically significant correlation of p53 with chemotherapy-resistance endpoints. The results from published clinical studies suggest a more complex role of p53 mutation in the mechanism of resistance in ovarian cancer than is suggested by in vitro studies.

The Role of Sense of Direction and Other Factors During Navigation in a Large-Scale, Unconstrained Environment

2013 ◽  
Author(s):  
Elisabeth J. Ploran ◽  
Ericka Rovira ◽  
James C. Thompson ◽  
Raja Parasuraman
Keyword(s):  
Large Scale ◽  
Sense Of Direction

Magnetic Properties of xCeO2•(50 − x) PbO•50B2O3 Glasses and Glass Ceramics

2017 ◽  
Vol 13 (1) ◽  
pp. 4486-4494 ◽  
Author(s):  
G.El Damrawi ◽  
F. Gharghar
Keyword(s):  
Magnetic Properties ◽  
Large Scale ◽  
Glass Ceramics ◽  
Magnetic Behavior ◽  
Crystal Formation ◽  
Dual Roles ◽  
Effective Agent ◽  
Ordered Structures ◽  
Essential Change

Cerium oxide in borate glasses of composition xCeO2·(50 − x)PbO·50B2O3 plays an important role in changing both microstructure and magnetic behaviors of the system. The structural role of CeO2 as an effective agent for cluster and crystal formation in borate network is clearly evidenced by XRD technique. Both structure and size of well-formed cerium separated clusters have an effective influence on the structural properties. The cluster aggregations are documented to be found in different range ordered structures, intermediate and long range orders are the most structures in which cerium phases are involved. The nano-sized crystallized cerium species in lead borate phase are evidenced to have magnetic behavior.  The criteria of building new specific borate phase enriched with cerium as ferrimagnetism has been found to keep the magnetization in large scale even at extremely high temperature. Treating the glass thermally or exposing it to an effective dose of ionized radiation is evidenced to have an essential change in magnetic properties. Thermal heat treatment for some of investigated materials is observed to play dual roles in the glass matrix. It can not only enhance alignment processes of the magnetic moment but also increases the capacity of the crystallite species in the magnetic phases. On the other hand, reverse processes are remarked under the effect of irradiation. The magnetization was found to be lowered, since several types of the trap centers which are regarded as defective states can be produced by effect of ionized radiation. 

The Impact of Quantitative Easing on Emerging Markets – Literature Review

e-Finanse ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 67-76
Author(s):  
Piotr Bartkiewicz
Keyword(s):  
Emerging Markets ◽  
Large Scale ◽  
Empirical Literature ◽  
Quantitative Easing ◽  
Methodological Choices ◽  
The Subject ◽  
Methodological Approaches ◽  
The Impact ◽  
Sufficient Precision

AbstractThe article presents the results of the review of the empirical literature regarding the impact of quantitative easing (QE) on emerging markets (EMs). The subject is of interest to policymakers and researchers due to the increasingly larger role of EMs in the world economy and the large-scale capital flows occurring after 2009. The review is conducted in a systematic manner and takes into consideration different methodological choices, samples and measurement issues. The paper puts the summarized results in the context of transmission channels identified in the literature. There are few distinct methodological approaches present in the literature. While there is a consensus regarding the direction of the impact of QE on EMs, its size and durability have not yet been assessed with sufficient precision. In addition, there are clear gaps in the empirical findings, not least related to relative underrepresentation of the CEE region (in particular, Poland).

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