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

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 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

Copy number variation of MDM2 and p53 genes in extracellular DNA as potential marker for lung adenocarcinoma diagnostics.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23094-e23094
Author(s):  
Denis S. Kutilin ◽  
Yaroslav S. Enin ◽  
Dmitriy I. Vodolazhsky ◽  
Vyacheslav A. Sustretov ◽  
Tamara G. Ayrapetova ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Copy Number ◽  
Gene Copy Number ◽  
P53 Gene ◽  
Extracellular Dna ◽  
Gene Copy ◽  
Mdm2 Gene ◽  
Healthy Donors ◽  
Number Variation ◽  
P53 Genes

e23094 Background: Today, the problem of early diagnostics of lung cancer remains unsolved as every fourth patient diagnosed with the disease already has distant metastases. Studying gene copy number variation (CNV) in extracellular DNA in the blood plasma can become a basis for a new effective and low invasive method for predictive diagnostics and disease prognosis. The purpose of the study was to examine the copy number of the MDM2 and p53 genes in extracellular DNA of patients with metastatic and non-metastatic lung cancer and healthy donors. Methods: The blood samples of 30 patients with lung adenocarcinoma (collected before surgery) and 30 healthy donors (without cancer) were studied. Each sample was centrifuged to obtain blood plasma. DNA was isolated from plasma using a phenol-chloroform extraction method. Detection of relative copy number of the MDM2 and p53 genes (reference gene - GAPDH) was performed by RT-qPCR using CFX96 thermocycler (Bio-Rad, USA). The groups were compared by the Mann-Whitney U- test. Results: Reduction of the p53 gene copy number by 57% (p < 0.05), as well as increasing of the MDM2 gene copy number by 160% (p < 0.05), were found in the extracellular DNA of patients with lung adenocarcinoma compared with healthy donors. As a result, the ratio of copy number of pro-/anti-apoptotic genes p53:MDM2 in extracellular DNA of patients with lung adenocarcinoma (1:23 ratio) was different from that of healthy donors (1:4 ratio). The MDM2 gene copy number in extracellular DNA of patients with metastases exceeded the value in non-metastatic patients two-fold (p < 0.05). The p53 gene copy number in extracellular DNA of patients with metastatic and non-metastatic cancer did not differ significantly. Conclusions: CNV of the p53 and MDM2 genes in extracellular DNA has a high potential for low invasive diagnostics and prognosis of lung adenocarcinoma.

scholarly journals Exploring the Effect of Differentially Expressed Long Non-coding RNAs Driven by Copy Number Variation on Competing Endogenous RNA Network by Mining Lung Adenocarcinoma Data

2021 ◽  
Vol 8 ◽  
Author(s):  
Huihui Hu ◽  
Hangdi Xu ◽  
Fen Lu ◽  
Jisong Zhang ◽  
Li Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Copy Number Variation ◽  
Drug Treatment ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Copy Number ◽  
Tumor Response ◽  
Competing Endogenous Rna ◽  
Number Variation ◽  
Non Coding Rnas

Lung cancer is the first cause of cancer death, and gene copy number variation (CNV) is a vital cause of lung cancer progression. Prognosis prediction of patients followed by medication guidance by detecting CNV of lung cancer is emerging as a promising precise treatment in the future. In this paper, the differences in CNV and gene expression between cancer tissue and normal tissue of lung adenocarcinoma (LUAD) from The Cancer Genome Atlas Lung Adenocarcinoma data set were firstly analyzed, and greater differences were observed. Furthermore, CNV-driven differentially expressed long non-coding RNAs (lncRNAs) were screened out, and then, a competing endogenous RNA (ceRNA) regulatory network related to the gene CNV was established, which involved 9 lncRNAs, seven microRNAs, and 178 downstream messenger RNAs (mRNAs). Pathway enrichment analyses sequentially performed revealed that the downstream mRNAs were mainly enriched in biological pathways related to cell division, DNA repair, and so on, indicating that these mRNAs mainly affected the replication and growth of tumor cells. Besides, the relationship between lncRNAs and drug effects was explored based on previous studies, and it was found that LINC00511 and LINC00942 in the CNV-associated ceRNA network could be used to determine tumor response to drug treatment. As examined, the drugs affected by these two lncRNAs mainly targeted metabolism, target of rapamycin signaling pathway, phosphatidylinositol-3-kinase signaling pathway, epidermal growth factor receptor signaling pathway, and cell cycle. In summary, the present research was devoted to analyzing CNV, lncRNA, mRNA, and microRNA of lung cancer, and nine lncRNAs that could affect the CNV-associated ceRNA network we constructed were identified, two of which are promising in determining tumor response to drug treatment.

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