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

Autor: Maxim N. Dyritsky, Vyacheslav A. Sustretov, Denis S. Kutilin, Oleg I. Kit, Dmitriy I. Vodolazhsky, Pavel A. Anistratov, Tamara G. Ayrapetova, Yaroslav S. Enin, Igor N. Turkin, Anna V. Chubaryan, Sergey P. Pyltsin, Igor A. Leyman, Leonid V. Kharin, Olesia A. Bogdanova
Rok vydání: 2017
Předmět:
Zdroj: Journal of Clinical Oncology. 35:e23094-e23094
ISSN: 1527-7755
0732-183X
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: