scholarly journals ZKSCAN3 Upregulation and Its Poor Clinical Outcome in Uterine Cervical Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2859 ◽  
Author(s):  
Sun Lee ◽  
Young-Eun Cho ◽  
Joo-Young Kim ◽  
Jae-Hoon Park
Keyword(s):  
Clinical Outcome ◽  
Gene Copy Number ◽  
Uterine Cervical Cancer ◽  
Gene Copy ◽  
Poor Clinical Outcome ◽  
Poor Overall Survival ◽  
Clinicopathological Findings ◽  
Frequent Event ◽  
Genes Encoding ◽  
Domain 3

Zinc finger with KRAB and SCAN domain 3 (ZKSCAN3) upregulates genes encoding proteins involved in cell differentiation, proliferation and apoptosis. ZKSCAN3 has been reported to be overexpressed in several human cancers such as colorectal cancer and prostate cancer and is proposed as a candidate oncoprotein. However, the molecular mechanism by which ZKSCAN3 participates in carcinogenesis is largely unknown. Here, we evaluated ZKSCAN3 expression in uterine cervical cancers (CC) by immunohistochemistry using formalin-fixed, paraffin-embedded tissues from 126 biopsy samples from 126 patients. The clinicopathological findings were analyzed and compared with ZKSCAN3 expression levels. ZKSCAN3 was strongly overexpressed in CCs compared to adjacent non-neoplastic cervical mucosa tissues. Moreover, a gene copy number assay showed amplified ZKSCAN3 in CC samples. ZKSCAN3 overexpression was also significantly associated with poor overall survival of the patients. Overall, our findings indicate that ZKSCAN3 overexpression is a frequent event in uterine CC and is correlated with a poor clinical outcome. ZKSCAN3 could be developed as a molecular marker for prognostic prediction and early detection.

Differential elimination of rDNA genes in bobbed mutants of Drosophila melanogaster

1986 ◽  
Vol 6 (4) ◽  
pp. 1023-1031
Author(s):  
R Terracol ◽  
N Prud'homme
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Copy Number ◽  
Rdna Locus ◽  
Gene Copy ◽  
Specific Gene ◽  
Type I ◽  
28S Rrna ◽  
Wild Type ◽  
Y Chromosomes ◽  
Genes Encoding

In Drosophila melanogaster, the multiply repeated genes encoding 18S and 28S rRNA are located on the X and Y chromosomes. A large percentage of these repeats are interrupted in the 28S region by insertions of two types. We compared the restriction patterns from a subcloned wild-type Oregon R strain to those of spontaneous and ethyl methanesulfonate-induced bobbed mutants. Bobbed mutations were found to be deficiencies that modified the organization of the rDNA locus. Genes without insertions were deleted about twice as often as genes with type I insertions. Type II insertion genes were not decreased in number, except in the mutant having the most bobbed phenotype. Reversion to wild type was associated with an increase in gene copy number, affecting exclusively genes without insertions. One hypothesis which explains these results is the partial clustering of genes by type. The initial deletion could then be due either to an unequal crossover or to loss of material without exchange. Some of our findings indicated that deletion may be associated with an amplification phenomenon, the magnitude of which would be dependent on the amount of clustering of specific gene types at the locus.

Optimization of Yarrowia lipolytica-based consolidated biocatalyst through synthetic biology approach: transcription units and signal peptides shuffling

2020 ◽  
Author(s):  
Ewelina Celińska ◽  
Monika Borkowska ◽  
Paulina Korpys-Woźniak ◽  
Monika Kubiak ◽  
Jean-Marc Nicaud ◽  
...  
Keyword(s):  
Gene Copy Number ◽  
Regulatory Elements ◽  
Gene Copy ◽  
Signal Peptides ◽  
Synthetic Dna ◽  
Batch Bioreactor ◽  
Genes Encoding ◽  
Valuable Compounds ◽  
Synthetic Biology Approach ◽  
Lipids Accumulation

Abstract Background: Nowadays considerable effort is being pursued towards development of consolidated microbial biocatalysts that will be able to utilize complex, non-pretreated substrates and produce valuable compounds. In such engineered microbes, synthesis of extracellular hydrolases may be fine-tuned by different approaches, like strength of promoter, type of secretory tag, gene copy number etc. In this study, we investigated if organization of a multi-element expression cassette impacts the resultant Y. lipolytica transformants’ phenotype, presuming that different variants of the cassette are composed of the same regulatory elements and encode the same hydrolases. Results: To this end, Y. lipolytica cells were transformed with expression cassettes bearing a pair of genes encoding exactly the same mature amylases, but fused to four different signal peptides (SP), and located interchangeably in either first or second position of a synthetic DNA construction. The resultant strains were tested for growth on raw and pre-treated complex substrates of different plant origin for comprehensive examination of the strains’ acquired characteristics. The best strain’s performance was tested in batch bioreactor cultivations for growth and lipids accumulation. Conclusions: Based on the conducted research we concluded that the positional order of transcription units (TU) and the type of exploited SP affect final characteristics of the resultant consolidated biocatalyst strains, and thus could be considered as additional factors to be evaluated upon consolidated biocatalysts optimization.

scholarly journals Gene copy number is associated with phytochemistry in Cannabis sativa

AoB Plants ◽  
2019 ◽  
Vol 11 (6) ◽  
Author(s):  
Daniela Vergara ◽  
Ezra L Huscher ◽  
Kyle G Keepers ◽  
Robert M Givens ◽  
Christian G Cizek ◽  
...  
Keyword(s):  
Copy Number ◽  
Cannabis Sativa ◽  
Sequence Data ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Multiple Points ◽  
Transcriptome Sequence Data ◽  
Cannabidiolic Acid ◽  
Genes Encoding ◽  
Genome Shotgun Sequence

Abstract Gene copy number (CN) variation is known to be important in nearly every species where it has been examined. Alterations in gene CN may provide a fast way of acquiring diversity, allowing rapid adaptation under strong selective pressures, and may also be a key component of standing genetic variation within species. Cannabis sativa plants produce a distinguishing set of secondary metabolites, the cannabinoids, many of which have medicinal utility. Two major cannabinoids—THCA (delta-9-tetrahydrocannabinolic acid) and CBDA (cannabidiolic acid)—are products of a three-step biochemical pathway. Using whole-genome shotgun sequence data for 69 Cannabis cultivars from diverse lineages within the species, we found that genes encoding the synthases in this pathway vary in CN. Transcriptome sequence data show that the cannabinoid paralogs are differentially expressed among lineages within the species. We also found that CN partially explains variation in cannabinoid content levels among Cannabis plants. Our results demonstrate that biosynthetic genes found at multiple points in the pathway could be useful for breeding purposes, and suggest that natural and artificial selection have shaped CN variation. Truncations in specific paralogs are associated with lack of production of particular cannabinoids, showing how phytochemical diversity can evolve through a complex combination of processes.

scholarly journals Differential elimination of rDNA genes in bobbed mutants of Drosophila melanogaster.

1986 ◽  
Vol 6 (4) ◽  
pp. 1023-1031 ◽  
Author(s):  
R Terracol ◽  
N Prud'homme
Keyword(s):  
Drosophila Melanogaster ◽  
Gene Copy Number ◽  
Rdna Locus ◽  
Gene Copy ◽  
Specific Gene ◽  
Type I ◽  
28S Rrna ◽  
Wild Type ◽  
Y Chromosomes ◽  
Genes Encoding

In Drosophila melanogaster, the multiply repeated genes encoding 18S and 28S rRNA are located on the X and Y chromosomes. A large percentage of these repeats are interrupted in the 28S region by insertions of two types. We compared the restriction patterns from a subcloned wild-type Oregon R strain to those of spontaneous and ethyl methanesulfonate-induced bobbed mutants. Bobbed mutations were found to be deficiencies that modified the organization of the rDNA locus. Genes without insertions were deleted about twice as often as genes with type I insertions. Type II insertion genes were not decreased in number, except in the mutant having the most bobbed phenotype. Reversion to wild type was associated with an increase in gene copy number, affecting exclusively genes without insertions. One hypothesis which explains these results is the partial clustering of genes by type. The initial deletion could then be due either to an unequal crossover or to loss of material without exchange. Some of our findings indicated that deletion may be associated with an amplification phenomenon, the magnitude of which would be dependent on the amount of clustering of specific gene types at the locus.

Gain of ALK gene copy number to predict lack of response to anti-EGFR treatment in advanced chemorefractory colorectal cancer (CRC) with KRAS/NRAS/BRAF/PI3KCA wild-type status.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3641-3641
Author(s):  
Filippo Pietrantonio ◽  
Anna Tessari ◽  
Rosalba Miceli ◽  
Pamela Biondani ◽  
Federica Perrone ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Copy Number ◽  
Response Rate ◽  
Gene Copy Number ◽  
Predictive Biomarkers ◽  
Gene Copy ◽  
Wild Type ◽  
Data Set ◽  
Exact Test ◽  
Need For Treatment

3641 Background: KRAS, BRAF, NRAS and exon 20 PIK3CA quadruple wild-type CRC is associated with 41.2% response rate to anti-EGFR treatments. Even in molecular characterized patients, there is still a subset of non responders. The identification of additional predictive biomarkers is an unmet clinical need for treatment personalization. Alterations of ALK oncoprotein may interfere with the biological activity of EGFR through cross-talk of downstream signalling pathways. Methods: This retrospective analysis aimed to investigate the correlation between ALK gene copy number (GCN), assessed by fluorescence in situ hybridization (FISH), and clinical outcome in KRAS/NRAS/BRAF/PI3KCA wild-type chemorefractory advanced CRC patients receiving cetuximab or panitumumab. FISH was perfomed with break-apart ALK (2p23) probes and gain of ALK GCN was defined as a mean of 3 to 5 signals in ≥10% of cells and amplification as ≥6 signals. Association of ALK status with RECIST response was performed by Fisher’s exact test. Results: Forty-one patients were identified, of whom 17 (41%) were ALK GCN positive, whereas the remaining 24 cases (59%) were ALK GCN negative. No ALK translocations were detected. Overall response rate was 19/41 (46%). We observed a partial response in 3/17 patients with ALK GCN positive versus 16/24 patients with ALK GCN negative (18% versus 67%, respectively; P=0.0036). Kaplan-meier curves for comparison of median progression-free and overall survival, as well as correlation with ALK expression by immunohistochemistry, will be presented at the Meeting exploring the whole National Cancer Institute data-set. Conclusions: In this study population with KRAS/NRAS/BRAF/PI3KCA wild-type tumors, the response rate greater than 40% is in line with literature data. ALK GCN may be a biomarker for clinical outcome prediction in advanced chemorefractory CRC patients treated with cetuximab or panitumumab.

scholarly journals Analysis of amplicons containing the esterase genes responsible for insecticide resistance in the peach-potato aphid Myzus persicae (Sulzer)

1996 ◽  
Vol 313 (2) ◽  
pp. 543-547 ◽  
Author(s):  
Linda M. FIELD ◽  
Alan L. DEVONSHIRE ◽  
Chris TYLER-SMITH
Keyword(s):  
Gene Amplification ◽  
Myzus Persicae ◽  
Gene Copy Number ◽  
Fold Increase ◽  
Gene Copy ◽  
Potato Aphid ◽  
Gene Copies ◽  
Genes Encoding ◽  
Aphid Clone ◽  
Peach Potato Aphid

The amplification of genes encoding an insecticide-detoxifying esterase (E4) in the peach-potato aphid Myzus persicae is one of the few examples where this genetic phenomenon has been shown to be involved in the response of an intact higher organism to artificial selection. Here we report quantitative and qualitative studies of the repeat units (amplicons) containing the E4 genes in a highly resistant aphid clone. Initial studies to quantify esterase sequences showed a 5-11-fold increase in resistant aphids compared with susceptible aphids, suggesting the presence of 10-22 gene copies per diploid genome. A more incisive analysis by pulsed-field gel electrophoresis confirmed the presence of about 12 copies of the E4 gene and showed them to be on about 24 kb amplicons, arranged as a tandem array of direct repeats. This, together with previous results from crossing experiments and with recent in situ hybridization studies, confirms that the E4 gene amplification in this aphid clone is heterozygous at a single locus. However, these data show that the gene amplification alone cannot account for the approx. 60 times higher levels of E4 protein and its mRNA present in this aphid clone, and therefore resistance must involve changes in both esterase gene copy number and gene expression.

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