Клиническое значение молекулярных маркеров — мутации BRAF V600E и делеции CDKN2A — при низкозлокачественных глиомах у детей: когортное исследование

Abstract

Background. Low-grade gliomas are the most common brain tumors in children. Gliomas have a favorable prognosis, but in some cases relapses or continued tumor growth occur. With relatively similar clinical and morphological characteristics of tumors, it is rather difficult to select a group of patients who may have progression. Objective. Our aim was to study the impact of certain clinical, histological and molecular characteristics of tumors on the progression/recurrence. Methods. A retrospective cohort study was carried out. Clinical data, histological features and molecular markers (overexpression of phosphorylated ERK1/2 (pERK1/2), mutation of B-Raf kinase (BRAF V600E), deletion of CDKN2A gene (delCDKN2A) were studied in 90 patients with low-grade pediatric gliomas, who were treated in the Center for Pediatric Oncology, Hematology and Immunology during 2010–2018. In gliomas with signs of anaplasia expression of gene of the X-linked alpha-thalassemia syndrome (ATRX), a trymethylated form of histone 3 (H3K27me), p53, and mutation of the dehydrogenase 1 isocitrate 1 gene (IDH1R132H) were also evaluated. Immunohistochemistry and the hybridization in situ (FISH) was performed to evaluate the molecular markers. Results. Statistical analysis confirmed the importance of such factors as non-radical tumor removal (p<0.0001), repeated treatment (p<0.0025), overexpression of pERK1/2 (p<0.0001), histological signs of anaplasia (p<0.0022), areas of diffuse growth (p<0.001), BRAF V600E (p<0.0001), delCDKN2A (p<0.0099). In tissue of gliomas with anaplasia overexpression of pERK1/2, mutation BRAF V600E, delCDKN2A and ATRX loss were more common. When conducting multivariate analysis, non-radical tumor removal and the presence of one of the molecular markers significantly influenced the prognosis (p<0.0001). Conclusion. The definition of molecular markers and the simultaneous assessment of the degree of tumor resection allows us to distinguish a group of patients with a high risk of tumor recurrence / progression.