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

The mutational landscape of circulating cell-free DNA to identify neoadjuvant chemotherapy response in colorectal cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15096-e15096
Author(s):  
Yanlong Liu ◽  
Xiaoli Wei ◽  
Xinying Shi ◽  
Ying Yang ◽  
Lili Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number Variation ◽  
Cancer Patients ◽  
Candidate Genes ◽  
Copy Number ◽  
Free Dna ◽  
Number Variation ◽  
Colorectal Cancer Patients ◽  
Response To Neoadjuvant Chemotherapy

e15096 Background: The neoadjuvant chemotherapy plays an important role in the current treatment of colorectal cancer (CRC), even though parts of patients could not be benefit from it. This study was aimed to explore the specific mutational profile of plasma cell free DNA (cfDNA) in CRC patients with or without response to neoadjuvant chemotherapy. Methods: 16 eligible CRC patients were enrolled in this study from Harbin Medical University Cancer Hospital. These patients were divided into two groups: with response ( R, n = 8) and without response (NR, n = 8) to neoadjuvant chemotherapy. All patients received neoadjuvant chemotherapy and their baseline blood samples were collected. The cfDNA fragments were extracted for enrichment of a panel covering exon regions of 1,086 genes. Gene alterations were analyzed to investigate the relationship between genetic characterizations of cfDNA and response to neoadjuvant chemotherapy. Results: Principal component (PCA) analysis for copy number variation(CNV) of cfDNA differed significantly in two groups. In the R group, there were higher frequency CNV loss in ABL-1, ERBB3, SMO, IGF1R, AURKA, PDGFRA, IDH1, BRAF, PIK3CB, NRAS, NF1, MITF, PTCH1 genes, and CNV gain in MTRR, HSP90AA1, VHL, CREBBP, CHEK2, DDR2, MUTYH, NCOA1, XPC, FANCA genes. Regarding to the area under the ROC curve, CNV of these genes had a high value of 0.967, which implied that CNV of the candidate genes have predictive value for identifying response to neoadjuvant chemotherapy in CRC patients. Furthermore, the Copy Number Instability (CNI) value of R group was significantly higher than NR group(p = 0.0014). Conclusions: The candidate genes’ copy number variation and CNI value of baseline plasma cfDNA can identify the colorectal cancer patients with response or without response to neoadjuvant chemotherapy in this small cohort. The molecular profile of cfDNA in plasma may be a potential biomarker for predicting the response to neoadjuvant chemotherapy in colorectal cancer patients. These findings warrant further expanded prospective cohorts to validate.

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).

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