GENES COPY NUMBER VARIATION INDEX IN CELL-FREE DNA OF BLOOD PLASMA AS A MARKER FOR LOW INVASIVE EFFICIENCY ASSESSMENT OF RECTAL TUMORS RADIOTHERAPY

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.

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THE EXTRACELLULAR DNA COPY NUMBER VARIATION INDEX OF GENES, REGULATES METABOLISM AND RECEPTION OF ESTROGENS AS POTENTIAL MARKER FOR HIGH-GRADE SEROUS OVARIAN ADENOCARCINOMA

Современные проблемы науки и образования (Modern Problems of Science and Education) ◽

10.17513/spno.30093 ◽

2020 ◽

pp. 12-12

Author(s):

M.R. Tsandekova

Keyword(s):

Copy Number Variation ◽

Copy Number ◽

Extracellular Dna ◽

High Grade ◽

Ovarian Adenocarcinoma ◽

Dna Copy Number Variation ◽

Potential Marker ◽

Number Variation ◽

Variation Index ◽

Serous Ovarian Adenocarcinoma

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GENES COPY NUMBER VARIATION INDEX AND RESISTANCE OF DIFFERENT NOSOLOGY TUMOR CELLS TO RADIATION

Современные проблемы науки и образования (Modern Problems of Science and Education) ◽

10.17513/spno.30111 ◽

2020 ◽

pp. 27-27

Author(s):

M.A. Gusareva ◽

M.S. Zinkovich ◽

N.G. Kosheleva ◽

A.A. Solntseva ◽

E.A. Karnaukhova ◽

...

Keyword(s):

Copy Number Variation ◽

Tumor Cells ◽

Copy Number ◽

Number Variation ◽

Variation Index

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Genes copy number as a marker of low-invasive assessment of rectal tumors radiotherapy effectiveness.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3025 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3025-3025

Author(s):

Marina A. Gusareva ◽

Natalia G Kosheleva ◽

Natalya B. Fatkina ◽

Anna A. Solntseva ◽

Lyudmila Ya. Rozenko ◽

...

Keyword(s):

Blood Plasma ◽

Copy Number ◽

Tumor Regression ◽

Extracellular Dna ◽

Molecular Characteristics ◽

Rectal Tumors ◽

Number Variation ◽

Group 2 ◽

Low Efficiency ◽

Group 1

3025 Background: Radiotherapy (RT) is a key component of rectal cancer (RC) treatment, however, nonresponsiveness in patients to preoperative RT is very common, usually due to the tumor cells radioresistance, mediated by their molecular characteristics, such as gene expression. The features of mRNA rapid degradation in extracellular environment make this indicator unsuitable for low invasive diagnostics. The solution to this problem is possible by switching to a more stable marker - the copy number variation (CNV), which can be determined in the extracellular DNA (cfDNA) circulating in the blood plasma. Therefore, the aim of the study was to identify the relationship between the level of genes CNV in the cfDNA of blood plasma with the effectiveness of rectal tumors RT. Methods: We used cfDNA preparations from blood plasma obtained before RT from 200 patients with RC, as well as from blood plasma of 50 apparently healthy donors (AHD, without cancer). RT was carried out on a linear accelerator Novalis TX (SFD = 2.4 Gy, TFD = 54.0 Gy). Blood samples were separated into plasma and cell fraction by centrifugation. Isolation of cfDNA from blood plasma was performed using the phenol-chloroform method. Determination CNV of 5 genes (BRCA2, H2AX, CASP9, RBBP8 and BCL2) was performed using Real-Time qPCR method. Differences were assessed using Mann-Whitney test; the Bonferroni correction was used to correct multiple comparisons. Results: RT results for 200 patients allowed them to be divided into 2 groups. After RT, 120 patients showed complete tumor regression (group 1), 50 patients showed insignificant tumor regression and 30 patients did not regress (group 2). In cfDNA of group 1 patients was found CNV decrease (p < 0.05) of H2AX and RBBP8 genes by 2.5 and 2.0 times, respectively, relative to AHD group. In the cfDNA of group 2patients an increase (p < 0.05) of BRCA2, H2AX, RBBP8 and BCL2 genes CNV was found by 2.0, 2.2, 2.0 and 2.0 times, respectively, relative to AHD group. Only 2 genes CNV differed in group 1 from group 2: the CNV of H2AX and RBBP8 was 5.4 and 4.0 times less respectively (p < 0.005). Conclusions: Thus, it has been found that increased CNV of genes BRCA2, H2AX, BCL2, RBBP8 in blood plasma cfDNA is associated with low efficiency of RT. At the same time, the CNV of H2AX and RBBP8 genes in cfDNA of patients with RC has the greatest potential as a marker of the RT effectiveness.

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