RESUMO
The 1p/19q codeletion is the result of a translocation between chromosome 1 (Chr1p) and chromosome 19 (Chr19q) with the loss of derivative (1;19)(p10;q10) chromosome. The 1p/19q codeletion has predictive and prognostic significance, and it is essential for the classification of gliomas. In routine practice, the fluorescence in situ hybridization (FISH) diagnosis of 1p/19q codeletion is sometimes unexpected. This study aimed to develop a next-generation sequencing panel for the concurrent definition of the 1p/19q codeletion and IDH1/IDH2 mutation status to resolve these equivocal cases. A total of 65 glioma samples were investigated using a 1p/19q-single-nucleotide polymorphism (SNP)-IDH panel. The panel consists of 192 amplicons, including SNPs mapping to Chr1 and Chr19 and amplicons for IDH1/IDH2 analysis. The 1p/19q SNP-IDH panel consistently identified IDH1/IDH2 mutations. In 49 of 60 cases (81.7%), it provided the same 1p/19q results obtained by FISH. In the remaining 11 cases, the 1p/19q SNP-IDH panel uncovered partial chromosome imbalances as a result of interstitial amplification or deletion of the regions where the FISH probes map, leading to a mistaken overdiagnosis of 1p/19q codeletion by FISH. The 1p/19q SNP-IDH next-generation sequencing panel allows reliable analysis of the 1p/19q codeletion and IDH1/IDH2 mutation at the same time. The panel not only allows resolution of difficult cases but also represents a cost-effective alternative to standard molecular diagnostics procedures.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 1/genética , Deleção de Genes , Glioma/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Hibridização in Situ Fluorescente/métodos , Isocitrato Desidrogenase/genética , Sobrediagnóstico , Translocação Genética/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Estudos de Coortes , Análise Custo-Benefício , Análise Mutacional de DNA/economia , Análise Mutacional de DNA/métodos , Feminino , Glioma/patologia , Sequenciamento de Nucleotídeos em Larga Escala/economia , Humanos , Hibridização in Situ Fluorescente/economia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/economia , Técnicas de Diagnóstico Molecular/métodos , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Although pleomorphic xanthoastrocytoma (PXA) is currently designed as a grade II glioma according to the WHO classification, a significant percentage of the tumors undergo malignant progression. In this study, the MGMT methylation status was examined in 11 PXA patients to determine if a biologic rationale exists to support the use of temozolomide (TMZ) for treatment of aggressive PXA. There were 9 cases of PXA grade II and 2 cases of PXA with anaplastic features. In the MGMT methylation study, only 2 (18.1%) of the 11 tumor samples tested by MS-qLNAPCR were positive for MGMT promoter methylation. In contrast, other cases, including PXAs with anaplastic features, were unmethylated. In addition, a tumor recurrence was found to be unmethylated. Thus, MGMT promoter methylation is not frequent in PXA and our results raise doubts about the benefits of treating indistinctly aggressive PXA with TMZ.