Genes copy number variation in tumor cells of patients with metastatic and non-metastatic lung adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14502-e14502 ◽  
Author(s):  
Denis S. Kutilin ◽  
Igor A. Leyman ◽  
Yuriy N. Lazutin ◽  
Anna V. Chubaryan ◽  
Pavel A. Anistratov ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Copy Number Variation ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Copy Number ◽  
Lung Tumor ◽  
Egfr Signaling Pathway ◽  
Copy Numbers ◽  
Metastatic Lung ◽  
Number Variation

e14502 Background: Currently known markers of lung adenocarcinoma are insufficient to predict the development of this disease, which makes the search for new molecular markers a relevant problem. Our purpose was to analyze changes in genes copy number variation (CNV) in tumor and non-tumor cells of the lung in patients with (T1-3N1-2M0-1) and without (T1-3N0M0) metastasis to identify potential molecular markers for the prediction of the disease development. Methods: The study was performed on tissue sections from FFPE blocks of 90 patients diagnosed with lung adenocarcinoma. Tumor and non- tumor cells were isolated using laser microdissection (Palm MicroBeam, Carl Zeiss). Copy numbers of 32 genes (BAX, BCL2, C-FLAR, P53, MDM2, BFAR, SEMA3B, RASSF1A, CASP9, CASP3, CASP8, SOX2, OCT4, NANOG, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, VEGFA, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, mir3678) were determined by Real-Time qPCR (ACTB, B2M, GAPDH - reference genes). Statistical analysis was performed using the Mann-Whitney test. Results: A pooled sample (n = 90) showed significant (p < 0.005) increase in the copy numbers of MAPK1 and SOX2 and decreased copy numbers of the mir3678, HV2, BAX and CASP3 genes in tumor cells compared to non-tumor. Patients with metastatic and non-metastatic lung adenocarcinoma had significant (p < 0.05) differences in genes copy number in tumor cells compared to non-tumor ones: patients with T1-3N1-2M0-1 (n = 50) – decreased copy numbers of the mir3678, HV2, MDM2, P53, XRCC1, CASP3 and OCT4 genes and increased SOX2 copy number; patients with T1-3N0M0 (n = 40) – increased copy numbers of the MAPK1 and mir3678 genes and decreased HV2 copy number. Conclusions: The detected changes in copy numbers of genes responsible for the regulation of apoptosis, proliferation, oxidative phosphorylation and the function of the EGFR signaling pathway in lung tumor cells revealed new molecular markers to predict the risk of metastasis ( mir3678, MDM2, Р53, SOX2, XRCC1, CASP3, OCT4, MAPK1).

Copy Number Variation in Tumor Cells and Extracellular DNA in Patients with Lung Adenocarcinoma

2019 ◽  
Vol 167 (6) ◽  
pp. 771-778 ◽  
Author(s):  
D. S. Kutilin ◽  
T. G. Airapetova ◽  
P. A. Anistratov ◽  
S. P. Pyltsin ◽  
I. A. Leiman ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Copy Number ◽  
Extracellular Dna ◽  
Number Variation

scholarly journals Salivary AMY1 Copy Number Variation Modifies Age-Related Type 2 Diabetes Risk

2020 ◽  
Vol 66 (5) ◽  
pp. 718-726
Author(s):  
Yuwei Liu ◽  
Caren E Smith ◽  
Laurence D Parnell ◽  
Yu-Chi Lee ◽  
Ping An ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Copy Number Variation ◽  
Metabolic Pathway ◽  
Copy Number ◽  
Lipid Lowering ◽  
Pathway Enrichment Analysis ◽  
Copy Numbers ◽  
Number Variation ◽  
The Relationship

Abstract Background Copy number variation (CNV) in the salivary amylase gene (AMY1) modulates salivary α-amylase levels and is associated with postprandial glycemic traits. Whether AMY1-CNV plays a role in age-mediated change in insulin resistance (IR) is uncertain. Methods We measured AMY1-CNV using duplex quantitative real-time polymerase chain reaction in two studies, the Boston Puerto Rican Health Study (BPRHS, n = 749) and the Genetics of Lipid-Lowering Drug and Diet Network study (GOLDN, n = 980), and plasma metabolomic profiles in the BPRHS. We examined the interaction between AMY1-CNV and age by assessing the relationship between age with glycemic traits and type 2 diabetes (T2D) according to high or low copy numbers of the AMY1 gene. Furthermore, we investigated associations between metabolites and interacting effects of AMY1-CNV and age on T2D risk. Results We found positive associations of IR with age among subjects with low AMY1-copy-numbers in both studies. T2D was marginally correlated with age in participants with low AMY1-copy-numbers but not with high AMY1-copy-numbers in the BPRHS. Metabolic pathway enrichment analysis identified the pentose metabolic pathway based on metabolites that were associated with both IR and the interactions between AMY1-CNV and age. Moreover, in older participants, high AMY1-copy-numbers tended to be associated with lower levels of ribonic acid, erythronic acid, and arabinonic acid, all of which were positively associated with IR. Conclusions We found evidence supporting a role of AMY1-CNV in modifying the relationship between age and IR. Individuals with low AMY1-copy-numbers tend to have increased IR with advancing age.

scholarly journals Plasmodium copy number variation scan: gene copy numbers evaluation in haploid genomes

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Johann Beghain ◽  
Anne-Claire Langlois ◽  
Eric Legrand ◽  
Laura Grange ◽  
Nimol Khim ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Gene Copy ◽  
Copy Numbers ◽  
Number Variation ◽  
Gene Copy Numbers

scholarly journals High levels of copy number variation of ampliconic genes across major human Y haplogroups

2017 ◽  
Author(s):  
Danling Ye ◽  
Arslan Zaidi ◽  
Marta Tomaszkiewicz ◽  
Corey Liebowitz ◽  
Michael DeGiorgio ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Y Chromosome ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Families ◽  
Digital Pcr ◽  
Gene Copy ◽  
Copy Numbers ◽  
Number Variation ◽  
Gene Copy Numbers

AbstractDue to its highly repetitive nature, the human male-specific Y chromosome remains understudied. It is important to investigate variation on the Y chromosome to understand its evolution and contribution to phenotypic variation, including infertility. Approximately 20% of the human Y chromosome consists of ampliconic regions which include nine multi-copy gene families. These gene families are expressed exclusively in testes and usually implicated in spermatogenesis. Here, to gain a better understanding of the role of the Y chromosome in human evolution and in determining sexually dimorphic traits, we studied ampliconic gene copy number variation in 100 males representing ten major Y haplogroups world-wide. Copy number was estimated with droplet digital PCR. In contrast to low nucleotide diversity observed on the Y in previous studies, here we show that ampliconic gene copy number diversity is very high. A total of 98 copy-number-based haplotypes were observed among 100 individuals, and haplotypes were sometimes shared by males from very different haplogroups, suggesting homoplasies. The resulting haplotypes did not cluster according to major Y haplogroups. Overall, only three gene families (DATZ, RBMY, TSPY) showed significant differences in copy number among major Y haplogroups, and the haplogroup of an individual could not be predicted based on his ampliconic gene copy numbers. Finally, we found a significant correlation between copy number variation and individual’s height (for three gene families), but not between the former and facial masculinity/femininity. Our results suggest rapid evolution of ampliconic gene copy numbers on the human Y, and we discuss its causes.

Copy number variation of genes in cell-free DNA in patients with lung adenocarcinoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24060-e24060
Author(s):  
Denis S. Kutilin ◽  
Igor N. Turkin ◽  
Dmitry I. Vodolazhsky ◽  
Tamara G. Ayrapetova ◽  
Sergey P. Pyltsin ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Number Variation

scholarly journals Evolutionary and functional analysis of RBMY1 gene copy number variation on the human Y chromosome

2019 ◽  
Vol 28 (16) ◽  
pp. 2785-2798 ◽  
Author(s):  
Wentao Shi ◽  
Sandra Louzada ◽  
Marina Grigorova ◽  
Andrea Massaia ◽  
Elena Arciero ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Y Chromosome ◽  
Sperm Motility ◽  
Copy Number ◽  
Population Variation ◽  
Gene Copy ◽  
Copy Numbers ◽  
Fish Samples ◽  
Number Variation ◽  
Fibre Fish

Abstract Human RBMY1 genes are located in four variable-sized clusters on the Y chromosome, expressed in male germ cells and possibly associated with sperm motility. We have re-investigated the mutational background and evolutionary history of the RBMY1 copy number distribution in worldwide samples and its relevance to sperm parameters in an Estonian cohort of idiopathic male factor infertility subjects. We estimated approximate RBMY1 copy numbers in 1218 1000 Genomes Project phase 3 males from sequencing read-depth, then chose 14 for valid ation by multicolour fibre-FISH. These fibre-FISH samples provided accurate calibration standards for the entire panel and led to detailed insights into population variation and mutational mechanisms. RBMY1 copy number worldwide ranged from 3 to 13 with a mode of 8. The two larger proximal clusters were the most variable, and additional duplications, deletions and inversions were detected. Placing the copy number estimates onto the published Y-SNP-based phylogeny of the same samples suggested a minimum of 562 mutational changes, translating to a mutation rate of 2.20 × 10−3 (95% CI 1.94 × 10−3 to 2.48 × 10−3) per father-to-son Y-transmission, higher than many short tandem repeat (Y-STRs), and showed no evidence for selection for increased or decreased copy number, but possible copy number stabilizing selection. An analysis of RBMY1 copy numbers among 376 infertility subjects failed to replicate a previously reported association with sperm motility and showed no significant effect on sperm count and concentration, serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels or testicular and semen volume. These results provide the first in-depth insights into the structural rearrangements underlying RBMY1 copy number variation across diverse human lineages.

scholarly journals Population differentiated copy number variation of Bos taurus, Bos indicus and their African hybrids

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jisung Jang ◽  
Kwondo Kim ◽  
Young Ho Lee ◽  
Heebal Kim
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Bos Taurus ◽  
Bos Indicus ◽  
Olfactory Receptors ◽  
Read Depth ◽  
Pathogen Resistance ◽  
Individual Level ◽  
Copy Numbers ◽  
Number Variation

Abstract Background CNV comprises a large proportion in cattle genome and is associated with various traits. However, there were few population-scale comparison studies on cattle CNV. Results Here, autosome-wide CNVs were called by read depth of NGS alignment result and copy number variation regions (CNVRs) defined from 102 Eurasian taurine (EAT) of 14 breeds, 28 Asian indicine (ASI) of 6 breeds, 22 African taurine (AFT) of 2 breeds, and 184 African humped cattle (AFH) of 17 breeds. The copy number of every CNVRs were compared between populations and CNVRs with population differentiated copy numbers were sorted out using the pairwise statistics VST and Kruskal-Wallis test. Three hundred sixty-two of CNVRs were significantly differentiated in both statistics and 313 genes were located on the population differentiated CNVRs. Conclusion For some of these genes, the averages of copy numbers were also different between populations and these may be candidate genes under selection. These include olfactory receptors, pathogen-resistance, parasite-resistance, heat tolerance and productivity related genes. Furthermore, breed- and individual-level comparison was performed using the presence or copy number of the autosomal CNVRs. Our findings were based on identification of CNVs from short Illumina reads of 336 individuals and 39 breeds, which to our knowledge is the largest dataset for this type of analysis and revealed important CNVs that may play a role in cattle adaption to various environments.

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