Prognostic significance of MDM2 gene expression in childhood neuroblastoma

• Дата: 2015
• Автори: Inomistova, M.V., Svergun, N.M., Khranovska, N.M., Skachkova, O.V., Gorbach, O.I., Klymnyuk, G.I.
• Формат: Стаття
• Мова: English
• Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2015
• Назва видання: Experimental Oncology
• Теми: Original contributions
• Онлайн доступ: http://dspace.nbuv.gov.ua/handle/123456789/145465
• Назва журналу: Digital Library of Periodicals of National Academy of Sciences of Ukraine
• Цитувати: Prognostic significance of MDM2 gene expression in childhood neuroblastoma / M.V. Inomistova, N.M. Svergun, N.M. Khranovska, O.V. Skachkova, O.I. Gorbach, G.I. Klymnyuk // Experimental Oncology. — 2015. — Т. 37, № 2. — С. 111-115. — Бібліогр.: 15 назв. — англ.

Aim: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma. Materials and Methods: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with ­Q-PCR analysis in fresh tumor samples and FISH in FFPE samples. Results: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan — Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization. Conclusion: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion. Key Words: neuroblastoma, MDM2 mRNA expression, MYCN gene amplification, p53/MDM2 interaction.