Molecular genetic features of neuroblastoma in adolescent
https://doi.org/10.17650/2313-805X-2024-11-2-106-115
Abstract
Aim. To determin the clinical and biological features of neuroblastoma in patients over 10 years old.
Materials and methods. Patients with a histologically verified diagnosis of neuroblastoma / ganglioneuroblastoma established over the age of 10 years were retrospectively selected. Molecular genetic tests included fluorescence in situ hybridization (FISH), multiplex ligation-dependent amplification (MLPA) and targeted next generation sequencing of tumor-derived DNA. The described cohort included 11 adolescents with histologically verified neuroblastoma / ganglioneuroblastoma with a median age of 160 months (124–173 months) at diagnosis and 1 patient aged 41 years (clinical data is missing). All adolescents were treated according to the neuroblastoma treatment protocol NB-2004. The median follow-up time for patients (n = 11) was 32 months (8–68 months).
Results. MYCN gene amplification was detected by FISH in 17 %; deletion of 1p and 11q – in 20 and 22.2 % of cases, respectively. Deletions of 1p and 3p (80 % cases each), 11q (67 % cases), 4p (56 % cases), and gain 17q (62.5 % cases) were frequently detected in tumors (n = 9) by MLPA. ATRX gene aberrations was found in 91.6 % (11 / 12). In the most cases (10 / 11; 90 %), ATRX gene deletions of varying length were detected. Missense substitutions p.V1678F, p.N2125I and nonsense mutation p.S213* were detected in 3 / 11 (27.3 %) patients. Moreover, in 2 patients, oncogenic nucleotide substitutions were identified in combination with ATRX gene deletion entire and monosomy X. Oncogenic genetic variants in components of the RAS-RAF-MEK (BRAF, NRAS, ALK) and p53 (ATM, TP53) pathways were detected in 58 % (7 / 12) of cases. No adverse events were observed when ALK inhibitors were added to first-line therapy in neuroblastomas harboring activating ALK mutations.
Conclusion. The clinical aggressiveness of adolescent / adult NB may be explained by the replicative immortalization of cells through alternative lengthening of telomeres, which is highlighted by ATRX aberrations. Special therapeutic recommendations should be elaborated for the treatment of patients in this age group, where special attention should be paid to the use of molecularly targeted therapy.
Supporting agencies: The study was carried out with the support of the Science for Children Foundation
About the Authors
N. A. Andreeva
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
Nataliya Alexandrovna Andreeva
117198; 1 Samora Mashela St.; Moscow
T. V. Shamanskaya
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
117198; 1 Samora Mashela St.; Moscow
D. Yu. Kachanov
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
117198; 1 Samora Mashela St.; Moscow
R. Kh. Abasov
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
117198; 1 Samora Mashela St.; Moscow
N. V. Gegeliya
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
117198; 1 Samora Mashela St.; Moscow
A. E. Druy
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia
Russian Federation
Russian Federation
117198; 1 Samora Mashela St.; Moscow
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Review
For citations:
Andreeva N.A., Shamanskaya T.V., Kachanov D.Yu., Abasov R.Kh., Gegeliya N.V., Druy A.E. Molecular genetic features of neuroblastoma in adolescent. Advances in Molecular Oncology. 2024;11(2):106-115. (In Russ.) https://doi.org/10.17650/2313-805X-2024-11-2-106-115
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