Email this article 
Innovative Technologies in Pediatric Neuro-Oncology
- Authors: Novichkova G.A.1, Papusha L.I.1, Druy A.E.1
-
Affiliations:
- D. Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
- Issue: Vol 78, No 5 (2023)
- Pages: 483-491
- Section: PEDIATRICS: CURRENT ISSUES
- URL: https://vestnikramn.spr-journal.ru/jour/article/view/15999
- DOI: https://doi.org/10.15690/vramn15999
- ID: 15999
Cite item
Open Access
Access granted
Abstract
At the present time pediatric neuro-oncology develops rapidly mostly due to the deep understanding of etiology and pathogenesis of the brain tumors in children, widespread introduction of molecular genetic technologies into diagnostic workflow and emergence of targeted therapeutic agents directing to the neoplastic cells. Many tumor entities undistinguishable at the level of histopathology were classified by the molecular techniques and now present as unique disorders. Clinical heterogeneity unraveled by molecular classification is a basis for modern risk stratification approaches. Variety of new tumor entities were discovered only because of implementation of advanced molecular diagnostics, which led to identification of the recurrent genetic aberration in neuroepithelial tumors with BCOR and PATZ1 genes alteration, intracranial mesenchymal tumors with FET-CREB rearrangements. The discovery of the targetable molecular drivers in gliomas allows the introduction of targeted therapies to the pediatric neuro-oncology with high results unreachable by other methods. In the current article we describe the experience of D. Rogachev National Medical Research Center in molecular diagnostics of pediatric brain tumors and targeted therapy in patients with different types of gliomas.
Full Text
About the authors
Galina A. Novichkova
D. Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Author for correspondence.
Email: gnovichkova@yandex.ru
ORCID iD: 0000-0002-2322-5734
SPIN-code: 7890-1419
д.м.н., профессор
Russian Federation, MoscowLudmila I. Papusha
D. Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Email: ludmila.mur@mail.ru
ORCID iD: 0000-0001-7750-5216
MD, PhD
Russian Federation, MoscowAlexander E. Druy
D. Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
Email: Dr-Drui@yandex.ru
ORCID iD: 0000-0003-1308-8622
SPIN-code: 9072-9427
MD, PhD
Russian Federation, MoscowReferences
- WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours of the Central Nervous System. 5th ed. Lyon: International Agency for Research on Cancer; 2021.
- Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123(4):465–472. doi: https://doi.org/10.1007/s00401-011-0922-z
- Pajtler KW, Mack SC, Ramaswamy V, et al. The current consensus on the clinical management of intracranial ependymoma and its distinct molecular variants. Acta Neuropathol. 2017;133(1):5–12. doi: https://doi.org/10.1007/s00401-016-1643-0
- Liu APY, Li BK, Pfaff E, et al. Clinical and molecular heterogeneity of pineal parenchymal tumors: a consensus study. Acta Neuropathol. 2021;141(5):771–785. doi: https://doi.org/10.1007/s00401-021-02284-5
- Hovestadt V, Ayrault O, Swartling FJ, et al. Medulloblastomics revisited: biological and clinical insights from thousands of patients. Nat Rev Cancer. 2020;20(1):42–56. doi: https://doi.org/10.1038/s41568-019-0223-8
- Друй А., Папуша Л., Сальникова Е., и др. Молекулярно-биологические характеристики медуллобластомы и их прогностическое значение // Вопросы онкологии. — 2017. — Т. 63. — № 4. — С. 536–544. [Druy AE, Papusha LI, Salnikova EA, et al. Molecular-biological features of medulloblastoma and their prognostic significance. Voprosy Onkologii = Problems in Oncology. 2017;63(4):536–544. (In Russ.)] doi: https://doi.org/10.37469/0507-3758-2017-63-4-536-544
- Appay R, Macagno N, Padovani L, et al. HGNET-BCOR Tumors of the Cerebellum: Clinicopathologic and Molecular Characterization of 3 Cases. Am J Surg Pathol. 2017;41(9):1254–1260. doi: https://doi.org/10.1097/PAS.0000000000000866
- Ferris SP, Velazquez Vega J, Aboian M, et al. High-grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication-a comprehensive clinical, radiographic, pathologic, and genomic analysis. Brain Pathol. 2020;30(1):46–62. doi: https://doi.org/10.1111/bpa.12747
- Zaytseva M, Papusha L, Panferova A, et al. Supratentorial tumor resembling anaplastic ependymoma in an adolescent. Brain Pathol. 2023;33(2):e13137. doi: https://doi.org/10.1111/bpa.13137
- Sloan EA, Gupta R, Koelsche C, et al. Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas. Brain Pathol. 2022;32(4):e13037. doi: https://doi.org/10.1111/bpa.13037
- Tabori U, Shlien A, Baskin B, et al. TP53 alterations determine clinical subgroups and survival of patients with choroid plexus tumors. J Clin Oncol. 2010;28(12):1995–2001. doi: https://doi.org/10.1200/JCO.2009.26.8169
- Zaytseva M, Valiakhmetova A, Yasko L, et al. Molecular heterogeneity of pediatric choroid plexus carcinomas determines the distinctions in clinical course and prognosis. Neuro Oncol. 2023;25(6):1132–1145. doi: https://doi.org/10.1093/neuonc/noac274
- Папуша Л.И., Зайцева М.А., Панферова А.В., и др. Анализ молекулярно-генетических аберраций у пациентов с глиомами низкой степени злокачественности: опыт НМИЦ ДГОИ им. Дмитрия Рогачева // Вопросы гематологии/онкологии и иммунопатологии в педиатрии. — 2022. — Т. 21. — № 1. — С. 12–18. [Papusha LI, Zaytseva MA, Panferova AV, et al. Analysis of genetic aberrations in pediatric low-grade gliomas: the experience of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Pediatric Hematology = Oncology and Immunopathology. 2022;21(1):12–18. (In Russ.)] doi: 10.24287/1726-1708-2022-21-1-12-18' target='_blank'>https://doi.org/doi: 10.24287/1726-1708-2022-21-1-12-18
- Ryall S, Zapotocky M, Fukuoka K, et al. Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas. Cancer Cell. 2020;37(4):569–583.e5. doi: https://doi.org/10.1016/j.ccell.2020.03.011
- Guerreiro Stucklin AS, Ryall S, Fukuoka K, et al. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas. Nat Commun. 2019;10(1):4343. doi: https://doi.org/10.1038/s41467-019-12187-5
- Papusha L, Zaytseva M, Panferova A, et al. Two clinically distinct cases of infant hemispheric glioma carrying ZCCHC8:ROS1 fusion and responding to entrectinib. Neuro Oncol. 2022;24(6):1029–1031. doi: https://doi.org/10.1093/neuonc/noac026
- Desai AV, Robinson GW, Gauvain K, et al. Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK, ROS1, or ALK aberrations (STARTRK-NG). Neuro Oncol. 2022;24(10):1776–1789. doi: https://doi.org/10.1093/neuonc/noac087
- Selt F, van Tilburg CM, Bison B, et al. Response to trametinib treatment in progressive pediatric low-grade glioma patients. J Neurooncol. 2020;149(3):499–510. doi: https://doi.org/10.1007/s11060-020-03640-3
- Zaytseva M, Usman N, Salnikova E, et al. Methodological Challenges of Digital PCR Detection of the Histone H3 K27M Somatic Variant in Cerebrospinal Fluid. Pathol Oncol Res. 2022;28:1610024. doi: https://doi.org/10.3389/pore.2022.1610024
Supplementary files
Supplementary Files
Action
1.
JATS XML
2.
Fig.1. A - uncontrolled hierarchical clustering of tumor samples based on targeted gene expression profiling allows us to identify medulloblastomas of the WNT (purple cluster), SHH (red cluster), group 3 (yellow cluster), group 4 (green cluster) and HG-NET BCOR (gray cluster) groups ); B - event-free survival of patients with medulloblastoma of various molecular groups (WNT - blue curve, SHH - red curve, group 3 - yellow curve, group 4 - green curve). Research method: NanoString expression profiling, n = 195
Download (215KB)
3.
Fig.2. Neuroepithelial tumor with PATZ1 gene rearrangement. A — hematoxylin-eosin staining (×100): a compact arrangement of ovoid tumor cells with the formation of perivascular pseudorosettes is noted; B — diffuse expression of GFAP (×200), punctate expression of EMA (×100, inset); B, transmission electron microscopy revealed a loose arrangement of cells, abundant stroma rich in fibrillar proteins, and the absence of intercellular contacts (×3000); D — schematic representation of the chimeric transcript MN1::PATZ1 identified using high-throughput RNA sequencing. ENST00000302326.5 and ENST00000266269.10 were used as reference transcripts for the MN1 and PATZ1 genes, respectively
Download (749KB)
4.
Fig.3. Uncontrolled hierarchical clustering of choroid plexus carcinoma samples from children based on targeted gene expression profiling allows us to identify two groups Ped_CPC1 (red cluster) and Ped_CPC2 (blue cluster). Black rectangles correspond to cases with the presence of mutations in the TP53 gene (solid circle fill - germinal mutation, circle outline - somatic mutation, × - mutation status unknown). Research method: NanoString expression profiling, n = 20
Download (269KB)
5.
Fig.4. Impact of TP53 gene status, karyotype and expression group on overall and event-free survival of pediatric patients with choroid plexus carcinomas of the brain
Download (206KB)
6.
Fig.5. Best tumor response during therapy with BRAF inhibitors and BRAF/MEK inhibitors in patients with gliomas with the presence of the BRAF V600E mutation. Response assessment based on magnetic resonance imaging of the brain, n = 24
Download (193KB)
7.
Fig.6. Best tumor response during MEK inhibitor monotherapy in patients with low-grade gliomas with the presence of the chimeric KIAA1549::BRAF transcript. Response assessment based on magnetic resonance imaging of the brain, n = 41
Download (216KB)
8.
Fig.7. A procedure for identifying diagnostic markers of midline brain tumors in cerebrospinal fluid, allowing to formulate an integral diagnosis within 7 hours
Download (217KB)
