RESUMO
BACKGROUND: Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types. OBJECTIVE: To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion. MATERIAL AND METHODS: We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma. RESULTS: Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery. CONCLUSION: Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.
Assuntos
Glioma , Neoplasias Neuroepiteliomatosas , Neoplasias Supratentoriais , Criança , Humanos , Proteínas de Ciclo Celular/genética , Metilação de DNA/genética , Fusão Gênica , Glioma/diagnóstico , Neoplasias Neuroepiteliomatosas/diagnóstico por imagem , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/cirurgia , Neoplasias Supratentoriais/diagnóstico por imagem , Neoplasias Supratentoriais/genética , Neoplasias Supratentoriais/cirurgia , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
BACKGROUND: Differential diagnosis of supratentorial ependymomas is of particular difficulty in neurooncology due to nonspecific clinical and radiographic findings, a rare seen «classic¼ morphological picture, and a nonspecific immunophenotype. Thanks to molecular genetic methods, in particular real-time PCR, it has become possible to verify supratentorial ependymomas and identify their molecular group, on which further prognosis depends. OBJECTIVE: To develop a set of molecular genetic tests based on real-time PCR to verify supratentorial ependymomas. MATERIAL AND METHODS: 56 tissue samples were collected from patients with supratentorial ependymomas, WHO Grade II, and anaplastic ependymomas, WHO Grade III. We developed primers and fluorescent TaqMan probes for real-time PCR analysis to detect the ZFTA::RELA, ZFTA::MAML2, ZFTA::NCOA2, ZFTA::MAML3, YAP1::MAMLD1, and YAP1::FAM118B gene fusions. For immunohistochemical analysis, monoclonal rabbit anti-NF-kb p65 antibodies (HUABIO, China) were used, the study was carried out on AutostainerLink 48 immunostainer (DAKO, Denmark). RESULTS: Real-time PCR was able to verify the diagnosis for 69.9% (n=39) of samples and classify them into molecular groups of ZFTA- or YAP1-positive supratentorial ependymomas. Immunohistochemically it was possible to verify 58% (n=29) ependymomas. CONCLUSION: Diagnosis by real-time PCR is a relatively fast, accessible and easily interpreted method that allows verification of the molecular group in 70% of cases of supratentorial ependymomas without the use of additional methods.
Assuntos
Ependimoma , Neoplasias Supratentoriais , Coelhos , Animais , Neoplasias Supratentoriais/diagnóstico , Neoplasias Supratentoriais/genética , Reação em Cadeia da Polimerase em Tempo Real , NF-kappa B/genética , Prognóstico , Ependimoma/diagnóstico , Ependimoma/genéticaRESUMO
Using the example of a recurrent tumor with a 10-year follow-up, the authors show that mutation of the IDH1/2 genes in astrocytomas is not always an early event in the pathogenesis of glioma, that in rare cases a 1p19q codeletion can be found in astrocytomas, and that IDH-mutant tumors can occur in childhood.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Astrocitoma/genética , Mutação , Isocitrato Desidrogenase/genéticaRESUMO
Identification of specific alterations in tumors (as a rule, these are mutations or gene fusions) makes it possible to prescribe targeted drugs of the second line of therapy or, in some cases of inoperable tumors, to observe not only a gradual partial response of the tumor to treatment, but also the removal of these patients from the category of incurable ones. The article describes a new rare type of BRAF::EPB41L2 gene fusion detected in a piloid astrocytoma that developed in the posterior cranial fossa in an 11-year-old boy.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Comunicação , Proteínas do Citoesqueleto , Fusão Gênica , Humanos , Masculino , Proteínas de Membrana , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Here we report three patients with rare primary intracranial sarcomas, two of them were CIC-sarcomas and one was a DICER1-sarcoma. Tumors were examined using DNA methylation. It is important to study of CIC fusions and DICER1 mutations in malignant brain tumors.
Assuntos
Neoplasias do Sistema Nervoso Central , Sarcoma , Neoplasias de Tecidos Moles , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , RNA Helicases DEAD-box/genética , Metilação de DNA , Humanos , Mutação , Ribonuclease III/genética , Sarcoma/diagnóstico , Sarcoma/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genéticaRESUMO
DnA methylation has recently been accepted as the most reliable and effective method of diagnosing central nervous system (CNS) tumors. Healthy organs and tumors of different localizations have their own unique methylation structure. Determination of total tumor DNA methylome is the detection of all methylated nucleotides in a tumor. The "gold standard" for analyzing the methylation state of individual cytosines is bisulfite conversion, in which unmethylated cytosines are converted to uracils and read as thymines, while methylated cytosines are protected from conversion.