scholarly journals Carcinosarcoma of the prostate: case report with molecular and histological characterization

2018 ◽  
Vol 33 (4) ◽  
pp. 540-544 ◽  
Author(s):  
Samanta Salvi ◽  
Valentina Casadio ◽  
Filippo Martignano ◽  
Giorgia Gurioli ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Copy Number Variations ◽  
Molecular Characteristics ◽  
Glutathione S Transferase ◽  
Molecular Alterations ◽  
Positive Expression ◽  
Molecular Pattern ◽  
Programmed Death ◽  
Number Variation

Background: We report a case of prostatic carcinosarcoma, a rare variant of prostatic cancer, which is composed of a mixture of epithelial and mesenchymal components with a generally poor outcome. Aims and methods: We aim to identify molecular alterations, in particular copy number variations of AR and c -MYC genes, methylation and expression of glutathione S-transferase P1 (GSTP1), programmed death-ligand 1 (PD-L1), AR, and phosphorylated AR expression. Results: We found a distinct molecular pattern between adenocarcinoma and carcinosarcoma, which was characterized by high AR copy number variation gain; positive expression of PD-L1, AR, and phosphorylated AR; low espression of GSTP1 in epithelial component. The sarcomatoid component had a lower gain of the AR gene, and no expression of PD-L1, AR, phosphorylated AR, or GSTP1. Both components had a gain of c-MYC copy number variation. Conclusions: Our findings suggest that carcinosarcoma has specific molecular characteristics that could be indicative for early diagnosis and treatment selection.

Application of Copy Number Variation Sequencing in Genetic Analysis of Miscarriages in Early and Middle Pregnancy

2020 ◽  
Vol 160 (11-12) ◽  
pp. 634-642
Author(s):  
Shiqiang Luo ◽  
Xingyuan Chen ◽  
Tizhen Yan ◽  
Jiaolian Ya ◽  
Zehui Xu ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
High Throughput ◽  
Copy Number ◽  
High Throughput Sequencing ◽  
Chromosomal Abnormalities ◽  
Pregnancy Termination ◽  
Mendelian Inheritance ◽  
Copy Number Variations ◽  
Abnormal Chromosome ◽  
Number Variation

High-throughput sequencing based on copy number variation (CNV-seq) is commonly used to detect chromosomal abnormalities. This study identifies chromosomal abnormalities in aborted embryos/fetuses in early and middle pregnancy and explores the application value of CNV-seq in determining the causes of pregnancy termination. High-throughput sequencing was used to detect chromosome copy number variations (CNVs) in 116 aborted embryos in early and middle pregnancy. The detection data were compared with the Database of Genomic Variants (DGV), the Database of Chromosomal Imbalance and Phenotype in Humans using Ensemble Resources (DECIPHER), and the Online Mendelian Inheritance in Man (OMIM) database to determine the CNV type and the clinical significance. High-throughput sequencing results were successfully obtained in 109 out of 116 specimens, with a detection success rate of 93.97%. In brief, there were 64 cases with abnormal chromosome numbers and 23 cases with CNVs, in which 10 were pathogenic mutations and 13 were variants of uncertain significance. An abnormal chromosome number is the most important reason for embryo termination in early and middle pregnancy, followed by pathogenic chromosome CNVs. CNV-seq can quickly and accurately detect chromosome abnormalities and identify microdeletion and microduplication CNVs that cannot be detected by conventional chromosome analysis, which is convenient and efficient for genetic etiology diagnosis in miscarriage.

scholarly journals Phenome-wide burden of copy number variation in UK Biobank

2019 ◽  
Author(s):  
Matthew Aguirre ◽  
Manuel Rivas ◽  
James Priest
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Significant Proportion ◽  
High Body Mass Index ◽  
Population Level ◽  
Copy Number Variations ◽  
Uk Biobank ◽  
Number Variation ◽  
Artery Disease ◽  
The Uk

AbstractCopy number variations (CNV) represent a significant proportion of the genetic differences between individuals and many CNVs associate causally with syndromic disease and clinical outcomes. Here, we characterize the landscape of copy number variation and their phenome-wide effects in a sample of 472,228 array-genotyped individuals from the UK Biobank. In addition to population-level selection effects against genic loci conferring high-mortality, we describe genetic burden from syndromic and previously uncharacterized CNV loci across nearly 2,000 quantitative and dichotomous traits, with separate analyses for common and rare classes of variation. Specifically, we highlight the effects of CNVs at two well-known syndromic loci 16p11.2 and 22q11.2, as well as novel associations at 9p23, in the context of acute coronary artery disease and high body mass index. Our data constitute a deeply contextualized portrait of population-wide burden of copy number variation, as well as a series of known and novel dosage-mediated genic associations across the medical phenome.

scholarly journals Frequency of CDK2 , CCNE1 Copy Number Variation in Acral Melanoma and Implications for CDK Inhibitor in Targeted Therapy

2020 ◽  
Author(s):  
Xiaowen Wu ◽  
Junya Yan ◽  
Jiayi Yu ◽  
Jinyu Yu ◽  
Zhiyuan Cheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Targeted Therapy ◽  
Copy Number Variation ◽  
Copy Number ◽  
Melanoma Cells ◽  
Copy Number Variations ◽  
Gene Copy ◽  
Cdk Inhibitor ◽  
Acral Melanoma ◽  
Number Variation

Abstract Background: Acral melanoma have a high frequency of cell cycle-related gene copy number variation. However, the status and clinical significance of CNVs of CDK 2 and CCNE1 have not been fully elucidated. Methods: A total of 490 acral melanoma samples were examined for CNVs of CDK 2 and CCNE1 using QuantiGenePlex DNA Assay. Correlations of CDK2 and CCNE1 CNVs to clinicopathologic features and prognosis of acral melanoma were evaluated.The sensitivity of cell lines and cell-derived xenograft (CDX) containing CCNE1 CNVs to CDK inhibitor AT7519,Dinaciclib and proteasome inhibitor Bortezomib were also analyzed. Results: Among the 490 samples,140 cases, 139 cases and 39 cases respectively showed CDK2 gain (28.5%), CCNE1 gain (28.3%) and CDK2 gain plus CCNE1 gain (8.0%).The median progression-free survival (PFS) time for acral patients with CCNE1 gain was significantly shorter than that for patients without CCNE1 gain (17.0 versus 27.0 months; P =0.002). Furthermore, CCNE1 gain was an independent prognostic factor for patients receiving chemotherapy. The pan-CDK inhibitor AT7519 could inhibit the cell proliferation, induce apoptosis and cause cell cycle arrest in G2 phase of acral melanoma cells and inhibit the tumor growth of CDX with CCNE1 gain. Dinaciclib and Bortezomib showed CCNE1 copy number independent inhibitory effects on the proliferation of melanoma cells. Conclusions: CDK2 and CCNE1 copy number variations were frequent in acral melanoma and CCNE1 gain may be a useful biomarker to predict the outcome of receiving chemotherapy in patients with acral melanoma. In addition, our study provides a basis for the use of CDK inhibitor in the treatment of acral melanoma. Keywords: acral melanoma, targeted therapy, CDK2 , CCNE1 , copy number variation

scholarly journals Adaptation by copy number variation increases insecticide resistance in fall armyworms

2019 ◽  
Author(s):  
Kiwoong Nam ◽  
Sylvie Gimenez ◽  
Frederique Hilliou ◽  
Carlos A. Blanco ◽  
Sabine Hänniger ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Insecticide Resistance ◽  
Host Plant ◽  
Copy Number ◽  
Host Plants ◽  
Fall Armyworm ◽  
Copy Number Variations ◽  
Main Challenge ◽  
Number Variation ◽  
Allelic Differentiation

AbstractInsecticide resistance is a major main challenge in pest control, and understanding its genetic basis is a key topic in agricultural ecology. Detoxification genes are well-known genetic elements that play a key role in adaptation to xenobiotics. The adaptive evolution of detoxification genes by copy number variations has been interpreted as a cause of insecticide resistance. However, the same pattern can be generated by the adaptation to host-plant defense toxins as well. In this study, we tested in fall armyworms (Lepidoptera Spodoptera frugiperda) if adaptation by copy number variation is the cause of the increased level of insecticide resistance from two geographic populations with different levels of resistance and two strains with different host plants. Following the generation of an assembly with chromosome-sized scaffolds (N50 = 13.2Mb), we observed that these two populations show a significant allelic differentiation of copy number variations, which is not observed between strains. In particular, a locus with almost complete allelic differentiation (Fst > 0.8) includes a cluster of P450 genes, which are well-known key players in detoxification. Detoxification genes are overrepresented in the genes with copy number variations, and the observed copy number variation appears to have beneficial effects in general. From this result, we concluded that copy number variation of detoxification genes in fall armyworms plays a key role in the insecticide resistance but not in the adaptation to host-plants, suggesting that the evolution of insecticide resistance may occur independently from host-plant adaptation.

BIOM-34. GENOMIC PROFILING IDENTIFIED COPY NUMBER VARIATIONS OF CDK4/6 AS A NOVEL PROGNOSTIC BIOMARKER FOR THALAMIC GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi18-vi18
Author(s):  
Mingyao Lai ◽  
zhaoming Zhou ◽  
Hainan Li ◽  
Jiangfen Zhou ◽  
Juan Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Copy Number Variation ◽  
Copy Number ◽  
Prognostic Biomarker ◽  
Gene Mutations ◽  
Copy Number Variations ◽  
Occurrence Rate ◽  
Number Variation ◽  
Thalamic Glioma ◽  
Astrocyte Differentiation

Abstract BACKGROUND Thalamic glioma is a rare tumor, which is poorly understood in adults. The genetic variation of this tumor is still unknown. In this study, we investigated the mutation landscape of thalamic glioma and compared the clinical outcomes between different mutation situations in thalamic glioma. METHODS Next-generation sequencing targeting 425 cancer-relevant genes was performed with 34 thalamic glioma tissue samples. Gene mutations and copy number variations were investigated for prognostic effect with overall survival data. RESULTS Several diagnostic and prognostic biomarkers appeared in our thalamic glioma cohort, including TP53 (56%), EGFR (41%), TERT (35%), M CL1 (26%), PDGFRA (26%), PTEN (26%), CDK4/6 (24%), POLE (24%), PIK3CA (24%), NF1 (21%), ATR (21%), ATRX (18%), BRAF (15%), and ROS1 (12%). Among all genetic aberrations with a more than 10% occurrence rate, two mutations (TERT and PTEN) were associated with poor overall survival and one copy number variation (CDK4/6) was associated with favorable overall survival (univariate P < 0.1). Among these genes, CDK4/6 copy number variations (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.035–0.704; P = 0.016) remained significant survival associated in multivariate analyses. Copy number variations of CDK4/6 was seldom reported as a prognostic biomarker for glioma, especially for thalamic glioma in public databases. Besides, several gene mutations (BRIP1, MRE11A, MAP2K1, ROS1, MUTYH, JARID2, CTCF, and EGFR) were found positively associated with CDK4/6 copy number variations. Gene enrichment analysis demonstrated that those genes were related to astrocyte differentiation. CONCLUSIONS In our study, CDK4/6 copy number variation was determined as a favorable overall survival biomarker for thalamic glioma, and CDK4/6 copy number variation associated mutant genes were related to astrocyte differentiation, which could be the potential therapeutic targets for thalamic glioma.

Identification and comprehensive characterization of lncRNAs with copy number variations and their driving transcriptional perturbed subpathways reveal functional significance for cancer

2019 ◽  
Vol 21 (6) ◽  
pp. 2153-2166 ◽  
Author(s):  
Yanjun Xu ◽  
Tan Wu ◽  
Feng Li ◽  
Qun Dong ◽  
Jingwen Wang ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
High Reliability ◽  
Copy Number Variations ◽  
Computational Method ◽  
Driving Mechanism ◽  
Cancer Hallmarks ◽  
Number Variation ◽  
Cancer Types ◽  
Comprehensive Characterization

Abstract Numerous studies have shown that copy number variation (CNV) in lncRNA regions play critical roles in the initiation and progression of cancer. However, our knowledge about their functionalities is still limited. Here, we firstly provided a computational method to identify lncRNAs with copy number variation (lncRNAs-CNV) and their driving transcriptional perturbed subpathways by integrating multidimensional omics data of cancer. The high reliability and accuracy of our method have been demonstrated. Then, the method was applied to 14 cancer types, and a comprehensive characterization and analysis was performed. LncRNAs-CNV had high specificity in cancers, and those with high CNV level may perturb broad biological functions. Some core subpathways and cancer hallmarks widely perturbed by lncRNAs-CNV were revealed. Moreover, subpathways highlighted the functional diversity of lncRNAs-CNV in various cancers. Survival analysis indicated that functional lncRNAs-CNV could be candidate prognostic biomarkers for clinical applications, such as ST7-AS1, CDKN2B-AS1 and EGFR-AS1. In addition, cascade responses and a functional crosstalk model among lncRNAs-CNV, impacted genes, driving subpathways and cancer hallmarks were proposed for understanding the driving mechanism of lncRNAs-CNV. Finally, we developed a user-friendly web interface-LncCASE (http://bio-bigdata.hrbmu.edu.cn/LncCASE/) for exploring lncRNAs-CNV and their driving subpathways in various cancer types. Our study identified and systematically characterized lncRNAs-CNV and their driving subpathways and presented valuable resources for investigating the functionalities of non-coding variations and the mechanisms of tumorigenesis.

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