Molecular genetic features of pediatric gliomas

Зайцева, М. А.; Ясько, Л. А.; Papusha, Ludmila; Druy, Alexander

doi:10.24287/1726-1708-2019-18-4-109-117

Cited by 4 publications

(4 citation statements)

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“…По данным A. Johnson и соавт., в серии из 90 ГБ аберрации H3F3A наблюдались в 43 (48 %) случаях, из них H3 K28M -в 35 (81 %), H3 G35R -в 8 (19 %) [2]. Кроме того, в исследованиях, посвященных изучению молекулярно-генетического профиля ВЗГ, подчеркивается, что для замен K28M и G35R / V харак терна корреляция с локализацией опухоли [2,3]. В глиомах срединных структур выявляется мутация H3 K28M, в глиомах полушарной локализации -H3 G35R / V. Данная особенность подтверждена и в серии наших наблюдений.…”

Section: экспериментальные статьиunclassified

“…Стоит отметить, что в зависимости от локализации точки разрыва могут возникать различные типы химерного гена ETV6-NTRK3. Вариант химерного транскрипта ETV6 (экзон 4) -NTRK3 (экзон 14) у детей с ВЗГ встречается заметно чаще [3,4,19].…”

Section: экспериментальные статьиunclassified

“…Определение мутационного статуса генов IDH1, IDH2, а также коделеции 1p / 19q стало необходимым для окончательной верификации гистологических вариантов глиом у взрослых пациентов, а определение мутации K28M в гене H3F3A стало обязательным для исключения диффузной срединной глиомы у детей, характеризующейся крайне агрессивным клиническим течением и неблагоприятным прогнозом [1]. Более того, после публикации классификации опухолей ЦНС ВОЗ 2016 г. была продемонстрирована диагностическая и прогностическая ценность многих других молекулярно-генетических аномалий, выявление которых в настоящее время активно применяется в рутинной практике и является неотъемлемым этапом окончательной постановки диагноза, а также определения тактики лечения пациентов с учетом генетического профиля опухоли [2][3][4][5].…”

Section: Introductionunclassified

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Analysis of genetic aberrations in pediatric high-grade gliomas

et al. 2020

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Background. High-grade gliomas are characterized by a wide range of genetic abnormalities. The heterogeneous genomic landscape of pediatric high-grade gliomas allows identifying distinct subgroups of the disease in children and young adults. Most importantly, these subgroups differ by clinical course and prognosis, as well as treatment response to standard therapy.Objective: to assess the profile of molecular genetic markers of high-grade gliomas in children.Materials and methods. In the current study, we examine the frequency of H3F3A, Hist1H3B, BRAF, IDH1 / 2 mutations, the copy number alterations of CDKN2A / 2B genes and the expression of ETV6‑NTRK3 fusion gene in a cohort of 53 pediatric high-grade gliomas.Results. Driver mutations and CDKN2A / 2B deletions were observed in 24 (45 %) and 15 (28 %) of 53 tumors, respectively. Overall, the studied high-grade gliomas harbored 41 genetic aberrations including 24 (58.5 %) somatic missense mutations, 1 (2.4 %) genetic variant of unknown clinical significance, 1 (2.4 %) oncogenic fusion gene and 15 (36.6 %) deletions of the tumor suppressor genes.Conclusion. These findings point to the importance of molecular profiling of tumors for the optimal clinical care and development of new approaches to treatment aimed at molecular targets for personalized anticancer therapies.

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Section: экспериментальные статьиunclassified

Section: Introductionunclassified

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Analysis of genetic aberrations in pediatric high-grade gliomas

et al. 2020

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“…Further studies of molecular landscapes of high-grade gliomas confirmed the high prevalence of H3 K27M variant in diffuse midline gliomas (DMG). This variant is observed in up to 94% of diffuse brainstem gliomas, 65% of thalamic gliomas, and 60% of spinal cord gliomas [ 4 ]. Moreover, the presence of H3 K27M mutation is a very unfavorable prognostic factor.…”

Section: Introductionmentioning

confidence: 99%

Methodological Challenges of Digital PCR Detection of the Histone H3 K27M Somatic Variant in Cerebrospinal Fluid

Zaytseva

Usman

Salnikova

et al. 2022

Pathol. Oncol. Res.

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Cell-free DNA (cfDNA) in body fluids is invaluable for cancer diagnostics. Despite the impressive potential of liquid biopsies for the diagnostics of central nervous system (CNS) tumors, a number of challenges prevent introducing this approach into routine laboratory practice. In this study, we adopt a protocol for sensitive detection of the H3 K27M somatic variant in cerebrospinal fluid (CSF) by using digital polymerase chain reaction (dPCR). Optimization of the protocol was carried out stepwise, including preamplification of the H3 target region and adjustment of dPCR conditions. The optimized protocol allowed detection of the mutant allele starting from DNA quantities as low as 9 picograms. Analytical specificity was tested using a representative group of tumor tissue samples with known H3 K27M status, and no false-positive cases were detected. The protocol was applied to a series of CSF samples collected from patients with CNS tumors (n = 18) using two alternative dPCR platforms, QX200 Droplet Digital PCR system (Bio-Rad) and QIAcuity Digital PCR System (Qiagen). In three out of four CSF specimens collected from patients with H3 K27M-positive diffuse midline glioma, both platforms allowed detection of the mutant allele. The use of ventricular access for CSF collection appears preferential, as lumbar CSF samples may produce ambiguous results. All CSF samples collected from patients with H3 wild-type tumors were qualified as H3 K27M-negative. High agreement of the quantitative data obtained with the two platforms demonstrates universality of the approach.

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