Раково-тестикулярным антигенам (РТА) свойственно проявление гетерогенности транскрипции в зависимости от клинико-патологических особенностей опухоли. Проведены многочисленные исследования экспрессии генов РТА (РТ-генов) в опухолях различных нозологий, однако экспрессия этих генетических локусов при раке толстой кишки изучена недостаточно хорошо. Целью исследования стал анализ транскрипционного профиля РТ-генов, характерных для опухолевой ткани толстой кишки пациентов с регионарными метастазами и без. Методом ПЦР в режиме реального времени выполнен анализ экспрессии 16 генов (MAGE-A1,

e16196 Background: Microsatellite instability (MSI), as an acquired feature of malignant tumors, is a predictive and prognostic marker. The less aggressive nature of MSI-positive tumors has been associated with high immunogenicity. In the present study, MSI was assessed in NET samples of different localizations. Methods: The sample included 50 patients with a diagnosis of pancreatic NET (G1-G3) and NET of colon (G2-G3). MSI was analyzed by fragment analysis of five microsatellite loci (Bat25, Bat26, NR21, NR24, NR27). The level of MLH1 methylation was detected by pyrosequencing. Results: MSI was noted in 25.8% cases of the NET of colon and in 13.3% cases of the NET of the pancreas. In the case of pancreatic NET, only MSI low level was identified (instability at 1/5 loci), while in the case of NET of colon, most cases were classified as MSI high level. The incidence of MSI of pancreatic NET was consistent with literature data for small intestinal NET (14%), unlike MSI NET and BRAF V600 mutated adenocarcinomas of colon, MSI-positive pancreatic NET were not associated with hypermethylation of the MLH1 promoter. MSI was more often detected in women over 60 years old, at stages of the tumor process without distant metastases (p = 0.49). The sample size did not allow us to determine significant differences in the studied clinical and pathological groups of NETs, however, we note that in all cases of an unfavorable course of the disease (progression, death), was noted MSS status of tumors. Conclusions: Thus, MSI-positive NET of colon resembles MSI-positive adenocarcinomas of colon in frequency and pathogenetic mechanisms, while in terms of the identified frequency of MSI in pancreatic NET resembles the NET of the small intestine.

Радиорезистентность опухолевых клеток, приводящая к неполному ответу опухоли на лечение, в настоящее время остается главной проблемой лучевой терапии злокачественных опухолей прямой кишки. За последние 30 лет был предложен ряд молекулярных маркеров в качестве предикторов ответа на лучевую терапию, однако ни один из них не вошел в клиническую практику. Соответственно, скрининг подобных маркеров остается актуальной задачей, для решения которой необходимо интегрировать данные по различным типам биомаркеров, полученным при проведении лучевой терапии по унифицированной схеме. Поэтому целью исследования стал поиск маркеров радиорезистентности опухолей прямой кишки на основании данных по вариации числа копий генов, экспрессии генов и микроРНК. В исследование было включено 75 больных раком прямой кишки и 30 условно-здоровых доноров. Лучевая терапия проводилось по схеме РОД = 2,4 Гр до СОД = 54 Гр на линейном ускорителе частиц Novalis TX. Показатели экспрессии генов и микроРНК определяли в образцах биопсии, показатель копийности -в образцах биопсии и внеклеточной ДНК методом Real-Time qPCR. Было показано, что эффективность лучевой терапии связана с аберрантной экспрессией 13 микро-РНК (

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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