e20542 Background: Lung cancer is the most common malignant tumor after breast cancer and is the main cause of cancer mortality. Mutations in the EGFR gene typical of lung cancer lead to constitutive activation of the epidermal growth factor receptor and malignant cell transformation. The purpose of this study was to identify associations between double and triple mutations in EGFR and clinical and pathological characteristics of patients in the South of Russia diagnosed with lung cancer. Methods: DNA was extracted from FFPE samples of 240 patients. Mutations in EGFR were detected using Cobas EGFR Mutation Test detection kit (Roche). Results: The mutant type of EGFR was identified in 24.6% of cases, and the most common activating mutations were ex19del (47.5%) and L858R (30.5%). Insertion in exon 20 was detected in 5.1% of mutation cases, G719X - in 3.4%. We also registered cases of identification of two or three mutations in one tumor: ex19del - L858R, ex19del - T790M, L858R - T790M with a frequency of 3.4% and G719X - ex20ins, ex19del - L858R - ex20ins with a frequency of 1.7%. Similar frequency is characteristic of the Caucasoid population of the USA. Multiple mutations in EGFR are associated with early manifestations of lung cancer and rapid progression of the disease. Two patients with two mutations EGFR T790M and L858R were of particular interest. According to the literature data, T790M is the most common somatic mutation that causes resistance to targeted therapy; however, rare cases could be associated with germinal variation of T790M. The primary T790M mutation is more common in patients with two or three mutations in EGFR. Conclusions: Mutations in the EGFR gene were detected in 24.6% of lung cancer cases in a patient population in the South of Russia. The frequency of two or three mutations in the EGFR gene was 0.33%. The timely detection of these mutations is particularly important for family cases when the risk group can be determined.

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e23503 Background: MMPs play a critical role in tumor growth and progression, metastatic development, angiogenesis, and tumor invasion. Epigenetic regulation of MMP2 and MMP9 levels is often disrupted in cancer and is considered as potential biomarkers. In this study, we tried to assess the methylation of the MMP2 and MMP9 genes in patients with localized and generalized forms of Ewing's sarcoma (ES). Methods: As a material used DNA from FFPE of primary tumor of 20 patients with localized forms ES and 20 patients with generalized forms ES. After bisulfite conversion of total DNA and PCR, the level of CpG methylation was assessed by sequencing on a Genetic Analyzer Applied Biosystems 3500. Results: The analysis showed the presence of hypomethylation of the MMP2 in the group with generalized forms (100%) 1.25 times more often than in the group with localized forms (80%), and hypermethylation was observed only in the group with localized forms–20% of cases (χ2 = 4.234, p = 0.040). On the other hand, hypermethylation was 1.9 times more common in the group with localized forms of ES (90%) (χ2 = 8.313, p = 0.004). Differences in the methylation status of the MMP2 and MMP9 indicate that the presence of hypomethylation at two loci increases the risk of developing generalized ES by 22 times (OR = 22.2, p < 0.05; CI95% 2.460-20.769). Conclusions: Specific methylation of the matrix metalloproteinases genes MMP2 and MMP9 identified in the groups of localized and generalized Ewing's sarcoma. At the same time, the group with generalized forms of ES was characterized by gene hypomethylation.

Рак яичников как одно из самых распространенных гинекологических онкозаболеваний отличается высоким процентом летальных исходов. В последнее время наблюдается рост популярности микроРНКтестов, основанных на измерении уровня экспрессии малых некодирующих РНК. Целью работы являлся поиск микроРНК-сигнатуры, с помощью которой можно с высокой степенью эффективности осуществлять прогнозирование и мониторинг серозного рака яичников. На основании данных the Cancer Genome Atlas (TCGA) были отобраны микроРНК, экспрессия которых ассоциирована с общей выживаемостью (ОВ) пациенток при раке яичников. В дальнейшем была набрана валидационная группа из 87 пациенток с верифицированным диагнозом «серозный рак яичников». На данном этапе методом RT-PCR валидировали результаты анализа TCGA и оценивали перспективы использования выбранных микроРНК в качестве прогностических маркеров. По результатам биоинформационного анализа выявлено 26 микроРНК, ассоциированных с ОВ. Методом логистической регрессии была определена микроРНК-сигнатура, для которой был рассчитан коэффициент risk score = (0.47 × RCQ hsa-miR-140-3p) + (-0.22 × RCQ hsa-miR-150-5p) + (0.26 × RCQ hsa-miR-221-3p). Качество теста, основанного на микроРНК сигнатуре, подтверждено с помощью валидационной когорты. Чувствительность теста для двухлетней выживаемости составила 92%, специфичность -98%. Результаты нашего исследования имеют практическую значимость и могут быть применены для стратификации больных в зависимости от риска рецидивирования и прогрессирования опухоли. Ключевые слова: рак яичников, hsa-miR-140-3p, hsa-miR-150-5p, hsa-miR-221-3p, общая выживаемость, The Cancer Genome Atlas.

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