Long-term survival of uveal melanoma patients after enucleation, depending on molecular genetic aberrations

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Цель работы-определить ассоциацию полиморфного маркера C3435T гена АBСB1 с риском развития начальной меланомы хориоидеи (НМХ) и изучить частоту распределения генотипов полиморфного гена ABCB1 у пациентов с НМХ. Материал и методы. В дизайне проспективного исследования обследовали 26 ранее не леченных пациентов с НМХ (7 мужчин и 19 женщин) в возрасте от 32 до 80 лет (средний возраст-59,0 ± 14,3 года). Всем пациентам проводили общеофтальмологические обследования и специальную инструментальную диагностику (ультразвуковое исследование, спектральную оптическую когерентную томографию, ОКТ-ангиографию). Монокулярная форма диагностирована у 25 (96 %) пациентов, бинокулярная форма-у 1 (4 %) пациента (всего 27 глаз). Материалом для исследования служила геномная ДНК, выделенная из лейкоцитов периферической крови пациентов с НМХ. Генотипирование осуществляли методом полимеразной цепной реакции с последующим анализом полиморфизма длины рестрикционных фрагментов (ПЦР-ПДРФ). Результаты. Показана статистически значимая ассоциация генотипа СС с риском развития НМХ и значимая связь генотипа ТТ гена ABCB1 с низким риском развития опухоли. Выявлена достоверная ассоциация генотипа СТ маркера C3435T гена АBСB1 с наличием очагов оранжевого пигмента на поверхности опухоли и отягощенным онкологическим семейным анамнезом больных НМХ. Заключение. Выявленные результаты в перспективе можно использовать для разработки современных подходов к прогнозированию течения НМХ, а также для скрининга пациентов. Ключевые слова: начальная меланома хориоидеи; молекулярно-генетическое исследование; ген MDR1/АBСB1 Конфликт интересов: отсутствует. Прозрачность финансовой деятельности: никто из авторов не имеет финансовой заинтересованности в представленных материалах или методах.

Section: Gnaq Gna11 Plcb4 Cysltr2 Sf3b1 Eif1axunclassified

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The role of the C3435T polymorphic marker of the ABCB1 gene in the development of early choroidal melanoma

Saakyan

Khlgatyan

Tsygankov

et al. 2020

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Long-term survival of uveal melanoma patients with respect to clinical, hemodynamic and morphological characteristics of the tumor

Saakyan

Amiryan

Tsygankov³

et al. 2022

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Purpose. Evaluation of long-term results of uveal melanoma (UM) treatment in patients depending on clinical, hemodynamic and morphological parameters of the tumor. Material and methods. Long-term results of treatment were analyzed in 394 UM patients aged 17 to 82 (mean age 53.1 ± 13.2). The median follow-up was 56 months. Group A (n = 242, organ-preserving treatment) consisted of patients with a tumor height of 5.0 ± 1.8 mm and base diameter of 12.7 ± 2.9 mm. Group B (n = 152, enucleation) included patients with 8.3 ± 2.8 mm tumor height and 15.2 ± 4.1 mm base diameter. Overall survival and disease-dependent survival were determined. Results. The cumulative 3-, 5-, and 7-year survival rates of patients with choroidal melanoma were 91.6 ± 1.7, 84.0 ± 2.5, 74.0 ± 3.8 % , and those with ciliochoroidal melanoma were 84.2 ± 5.6, 79.9 ± 5.8, and 53.0 ± 14.7 %, respectively (p = 0.048). In group A, the 5-year survival rates of patients with mushroom-shaped and irregular forms were 80.6 ± 5.9 and 74.6 ± 10.9 %, respectively, and 96.0 ± 2.0 % for dome-shaped UM. The worst 5-year survival rates were shown by patients with tumor stabilization, and the best ones, by patients with complete tumor resorption (x2 = 6.880, p = 0.008). Patients with post-radiation optical neuropathy (n = 193) had better 5-year survival rates (90.3 ± 2.9 %) than patients (n = 49) without neuropathy (77.5 ± 8.0 %). In group B, cumulative 1-year survival was 95.2 ± 1.9 %, 2-year survival, 89.2 ± 2.8 % , 3-year survival, 84.9 ± 2.9 % , 4-year survival, 81.8 ± 3.6 %, 5-year survival, 77.5 ± 4.0 % , 6-year survival, 67.9 ± 4.8 % , and 7-year survival was 64.7 ± 5.2 %. In epithelioid-cell, mixed-cell, and spindle-cell types of UM, the 5-year survival rates were 46.3 ± 12.0, 70.7 ± 8.0 %, and 84.8 ± 5.4 %, respectively (x2 = 11.571, p = 0.004). The 5-year survival rate of patients with extrascleral growth was 56.0 ± 10.4 % and without extrascleral growth it was 81.7 ± 4.0 %. Conclusion. In organ-preserving treatment, the combination of prognostic factors allows us to stratify the patients based on the risk of early metastasis, which allows for personalized dynamic monitoring, taking into account the vital prognosis of a particular patient.

Association of clinical-morphological and molecular-genetic factors (mutations in GNAQ and GNA11 oncogenes and АBСB1 gene polymorphism) in patients with iris melanoma

Saakyan,

Svirina,

Tsygankov

et al. 2024

Purpose: to analyze the frequency of GNAQ/GNA11 mutations in circulating tumor DNA and tumor tissue, and the frequency of genotypes of polymorphic marker C3435T of ABCB1 gene in patients with iris melanoma. Material and methods. The study included 139 patients with uveal melanoma (UM) followed in 2011–2023. The experimental group included 46 patients with iris melanoma (n = 20, group I) and ciliary body involvement (n = 26, group II), who underwent a molecular genetic study. The comparison group III consisted of 30 UM patients managed in 2012. Morphologically, uveal melanoma was verified in all cases. Results. No mutations in the GNAQ/GNA11 genes were identified in group I. In group II, one heterozygous mutation in the GNAQ/GNA11 genes was detected in 2 patients (7.7 %). No significant associations with clinical or pathomorphological features were found (p > 0.1). In the comparison group III, mutations in the GNAQ/ GNA11 genes were detected in 27 patients (90 %). When comparing the frequency of heterozygous mutations in the GNAQ/ GNA11 genes significant differences between the experimental groups and the comparison group were revealed (F = 0.0000001, χ2 = 56.45). The CC genotype of the C3435T polymorphic marker of the ABCB1 gene was found in 90 % (F = 0.026418, χ2 = 5.36, significantly more frequently than in group III), in group II — in 92.3 % (F = 0.006183, χ2 = 7.75, significantly more frequently than in group III), in group III it was found in 60 %. The TT genotype was not detected in any group. Conclusion. This study has shown that the frequency of mutations in GNAQ and GNA11 genes, the frequency of CT genotype of ABCB1 polymorphic marker C3435T gene in iris melanoma is significantly lower than that in choroid melanoma, indicating a relatively favorable tumor behaviour.