Correlation analysis of gene and immune microenvironment for 87 melanoma cases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21555-e21555
Author(s):  
Lanqun Qin ◽  
Yu Ren ◽  
Lianjun Zhao ◽  
Yirong Wu ◽  
Mengke Zhao ◽  
...  
Keyword(s):  
Copy Number ◽  
Poor Prognosis ◽  
Gene Copy Number ◽  
Primary Melanoma ◽  
Gene Copy ◽  
Immune Microenvironment ◽  
Braf Mutations ◽  
Melanoma Patients ◽  
The Difference ◽  
Copy Number Amplification

e21555 Background: To map the genome of Chinese melanoma patients and explore its correlation with the expression of tumor immune microenvironmental indicators. Methods: Next generation sequencing was performed on 87 cases of primary melanoma that had been surgically removed from Nanjing Drum Tower Hospital from July 2010 to May 2017. Immunohistochemistry was carried out to detect the expressions of PD1, PDL1, CD3+TIL, MSH2, MSH6, PMS2 and MLH1. Results: BRAF mutations were the most common (26.4%), followed by KIT mutations (12.6%) in melanoma patients. RB1 gene copy number deletion (55%) and CDK4 (25%)/CCND1 (22.5%) gene copy number amplification were also common. The prognosis of patients could be distinguished by grouping the expression of PDL1 and TIL, and the difference may be related to the expression of PD1. There were more copy number amplication of genes with poor prognosis in PDL1-TIL- patients. Conclusions: The classification of tumors into four microenvironmental subtypes based on PDL1 and TIL expression is an appropriate method to stratify patients with different clinical outcomes. At the genetic level, there are more copy number amplification of the genes with poor prognosis in patients with TIL-PDL1- type, so the prognosis is always worse than that of patients with TIL+PDL1+ type. Gene may affect the prognosis of patients by affecting the tumor immune microenvironment.

scholarly journals Top-level MET gene copy number gain defines a subtype of poorly differentiated pulmonary adenocarcinomas with poor prognosis

2020 ◽  
Vol 9 (3) ◽  
pp. 603-616 ◽  
Author(s):  
Tobias Raphael Overbeck ◽  
Dana Alina Cron ◽  
Katja Schmitz ◽  
Achim Rittmeyer ◽  
Wolfgang Körber ◽  
...  
Keyword(s):  
Copy Number ◽  
Poor Prognosis ◽  
Gene Copy Number ◽  
Copy Number Gain ◽  
Gene Copy ◽  
Poorly Differentiated ◽  
Gene Copy Number Gain

scholarly journals Emergence of a Viral RNA Polymerase Variant during Gene Copy Number Amplification Promotes Rapid Evolution of Vaccinia Virus

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Trade Offs ◽  
Number Variation ◽  
Copy Number Amplification

ABSTRACT Viruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution encoded within A24R conferred fitness trade-offs, including increased activation of the antiviral factor protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We showed that the sweep of this variant could be accelerated by the presence of copy number variation (CNV) at the K3L locus, which in multiple copies strongly reduced PKR activation. Therefore, adaptive cases of CNV can facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses. IMPORTANCE Viruses can evolve quickly to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations emerge in populations at the same time. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R and, surprisingly, found that one of these mutations activates the nucleic acid sensing factor PKR. We also found that gene copy number variation (CNV) can provide dual benefits to evolving virus populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accelerate the fixation of mutations conferring modest benefits, or even fitness trade-offs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect actions.

scholarly journals Directed gene copy number amplification inPichia pastorisby vector integration into the ribosomal DNA locus

2009 ◽  
Vol 9 (8) ◽  
pp. 1260-1270 ◽  
Author(s):  
Hans Marx ◽  
Astrid Mecklenbräuker ◽  
Brigitte Gasser ◽  
Michael Sauer ◽  
Diethard Mattanovich
Keyword(s):  
Ribosomal Dna ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Vector Integration ◽  
Copy Number Amplification

scholarly journals Accelerated selection of a viral RNA polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus

2016 ◽  
Author(s):  
Kelsey R. Cone ◽  
Zev N. Kronenberg ◽  
Mark Yandell ◽  
Nels C. Elde
Keyword(s):  
Rna Polymerase ◽  
Vaccinia Virus ◽  
Copy Number ◽  
Point Mutations ◽  
Gene Copy Number ◽  
Viral Rna ◽  
Gene Copy ◽  
Number Variation ◽  
Fitness Tradeoffs ◽  
Copy Number Amplification

AbstractViruses are under relentless selective pressure from host immune defenses. To study how poxviruses adapt to innate immune detection pathways, we performed serial infections of vaccinia virus in primary human cells. Independent courses of experimental evolution with a recombinant strain lacking E3L revealed several high frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. Two distinct mutations were identified in the viral RNA polymerase gene A24R, which seem to act through different mechanisms to increase virus replication. Specifically, a Leu18Phe substitution in A24R conferred fitness tradeoffs, including increased activation of the antiviral factor Protein kinase R (PKR). Intriguingly, this A24R variant underwent a drastic selective sweep during passaging, despite enhanced PKR activity. We show that the sweep of this variant can be accelerated by the presence of copy number variation (CNV) at the K3L locus, which with multiple copies strongly reduces PKR activation. Therefore, adaptive cases of CNV can also facilitate the accumulation of point mutations separate from the expanded locus. This study reveals how rapid bouts of gene copy number amplification during accrual of distant point mutations can potently facilitate poxvirus adaptation to host defenses.ImportanceViruses can quickly evolve to defeat host immune functions. For poxviruses, little is known about how multiple adaptive mutations might concurrently emerge in populations. In this study, we uncovered a means of vaccinia virus adaptation involving the accumulation of distinct genetic variants within a single population. We identified adaptive point mutations in the viral RNA polymerase gene A24R, and show that these mutations can affect the activation of host nucleic acid sensing pathways through different mechanisms. We also found that structural variants within viral genomes in the form of gene copy number variation (CNV) provide dual benefits to evolving populations, including evidence that CNV facilitates the accumulation of a point mutation distant from the expanded locus. Our data suggest that transient CNV can accommodate the accumulation of mutations conferring modest benefits, or even fitness tradeoffs, and highlight how structural variation might aid poxvirus adaptation through both direct and indirect action.

scholarly journals EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis

2007 ◽  
Vol 121 (8) ◽  
pp. 1729-1737 ◽  
Author(s):  
Zsuzsa Rákosy ◽  
Laura Vízkeleti ◽  
Szilvia Ecsedi ◽  
Zoltán Vokó ◽  
Ágnes Bégány ◽  
...  
Keyword(s):  
Copy Number ◽  
Poor Prognosis ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Copy Number Alterations ◽  
Egfr Gene ◽  
Malignant Melanomas

Evidence for frequent concurrent DCUN1D1, FGFR1, BCL9 gene copy number amplification in Squamous Cell Lung Cancer

2021 ◽  
pp. 153412
Author(s):  
Ilenia Chatziandreou ◽  
Adriana Psaraki ◽  
Konstantinos Paschidis ◽  
Andreas C. Lazaris ◽  
Angelica A. Saetta
Keyword(s):  
Lung Cancer ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Squamous Cell Lung Cancer ◽  
Gene Copy ◽  
Copy Number Amplification

scholarly journals Impact of Gene Copy Number Variation on Anesthesia in Drosophila melanogaster 

2009 ◽  
Vol 111 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Debasmita P. Alone ◽  
Jason C. Rodriguez ◽  
Cameron L. Noland ◽  
Howard A. Nash
Keyword(s):  
Drosophila Melanogaster ◽  
Copy Number Variation ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Gene Copy Number Variation ◽  
Number Variation ◽  
Righting Reflex ◽  
The Difference ◽  
Average Size

Background Chromosomal deletions and duplications, which result in halving or doubling of copy number in a block of genes, are an important source of variation between individuals. Phenotypic effects of copy number variation are commonly observed, but effects on sensitivity to volatile anesthetics have not been assessed in any organism. Methods The potency with which halothane depresses the righting reflex of fruit flies was measured in congenic Drosophila strains, each of which was heterozygous for a deletion of average size 400 kb. Over 200 strains were examined, thereby scanning approximately half of the fly genome. Results Although the vast majority of deletion heterozygotes were indistinguishable from the control, eight had significantly altered sensitivity to halothane. Genetic tests supported the hypothesis that the change in anesthetic sensitivity was the result of reduction in copy number and not adventitious mutations in the strains. Among the eight outliers, the difference in halothane potency ranged from a 25% increase to a 15% decrease. Changes of similar magnitude but distinctive patterns were found when these lines were tested with enflurane, isoflurane, and sevoflurane. Conclusions Variation in gene copy number has a significant impact on anesthetic sensitivity in Drosophila melanogaster. The level of transcription of a few genes must thus be limiting for a normal response to volatiles. Coupling between gene copy and gene expression is universal, and the components of the fly's nervous system are highly conserved; therefore, this work provides a rationale for investigating the clinical impact of copy number variation.

scholarly journals Amylasecopy number analysis in several mammalian lineages reveals convergent adaptive bursts shaped by diet

2018 ◽  
Author(s):  
Petar Pajic ◽  
Pavlos Pavlidis ◽  
Kirsten Dean ◽  
Lubov Neznanova ◽  
Erin Daugherity ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Copy Number ◽  
Mammalian Species ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Adaptive Mechanism ◽  
Amylase Gene ◽  
Present Evidence ◽  
Copy Number Amplification

AbstractThe amylase gene (AMY), which codes for a starch-digesting enzyme in animals, underwent several gene copy number gains in humans1, dogs2, and mice3, presumably along with increased starch consumption during the evolution of these species. Here we present evidence for additionalAMYcopy number expansions in several mammalian species, most of which also consume starch-rich diets. We also show that these independentAMYcopy number gains are often accompanied by a gain in enzymatic activity of amylase in saliva. We used multi-species coalescent modeling to provide further evidence that these recurrentAMYgene copy number expansions were adaptive. Our findings underscore the overall importance of gene copy number amplification as a flexible and fast adaptive mechanism in evolution that can independently occur in different branches of the phylogeny.

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