Abstract
The updated 2016 World Health Organization (WHO) classification system for gliomas integrates molecular alterations and histology to provide a greater diagnostic and prognostic utility than the previous, histology-based classification. The increasing number of markers that are tested in a correct diagnostic procedure makes gene-targeted, next-generation sequencing (NGS) a powerful tool in routine pathology practice. We designed a 14-gene NGS panel specifically aimed at the diagnosis of glioma, which allows simultaneous detection of mutations and copy number variations, including the 1p/19q-codeletion and Epidermal Growth Factor Receptor (EGFR) amplification. To validate this panel, we used reference mutated DNAs, nontumor and non-glioma samples, and 52 glioma samples that were previously characterized. The panel was then prospectively applied to 91 brain lesions. A specificity of 100% and sensitivity of 99.4% was achieved for mutation detection. Orthogonal methods, such as in situ hybridization and immunohistochemical techniques, were used for validation, which showed high concordance. The molecular alterations that were identified allowed diagnosis according to the updated WHO criteria, and helped in the differential diagnosis of difficult cases. This NGS panel is an accurate and sensitive method, which could replace multiple tests for the same sample. Moreover, it is a rapid and cost-effective approach that can be easily implemented in the routine diagnosis of gliomas.
Highlights
Studies performed by the scientific community over the past two decades have substantially clarified the genetic basis of tumorigenesis in both common and some rarer central nervous system (CNS) tumor entities [1,2,3,4]
We describe the validation of a custom glioma next-generation sequencing (NGS)-targeted panel that was developed at our institution to simultaneously detect both relevant glioma-related gene mutations and copy number variations (CNVs)
We report a good correlation between the detection of a 1p/19q loss by fluorescence in situ hybridization (FISH) and the presence of loss of heterozygosity (LOH), as determined by our NGS panel
Summary
Studies performed by the scientific community over the past two decades have substantially clarified the genetic basis of tumorigenesis in both common and some rarer central nervous system (CNS) tumor entities [1,2,3,4]. This improved understanding of brain tumors contributes to their classification and identifies molecular biomarkers that are useful in the diagnosis, prognosis, and therapeutic approach for treating patients with CNS tumors. We report here our one-year experience of clinical practice using this targeted glioma NGS panel to guide diagnosis
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