A Targeted Next-Generation Sequencing Panel to Genotype Gliomas.
Maria GuarnacciaLaura GuarnacciaValentina La CognataStefania Elena NavoneRolando CampanellaAntonella AmpolliniMarco LocatelliMonica MiozzoGiovanni MarfiaSebastiano CavallaroPublished in: Life (Basel, Switzerland) (2022)
Gliomas account for the majority of primary brain tumors. Glioblastoma is the most common and malignant type. Based on their extreme molecular heterogeneity, molecular markers can be used to classify gliomas and stratify patients into diagnostic, prognostic, and therapeutic clusters. In this work, we developed and validated a targeted next-generation sequencing (NGS) approach to analyze variants or chromosomal aberrations correlated with tumorigenesis and response to treatment in gliomas. Our targeted NGS analysis covered 13 glioma-related genes ( ACVR1 , ATRX , BRAF , CDKN2A , EGFR , H3F3A , HIST1H3B , HIST1H3C , IDH1 , IDH2 , P53 , PDGFRA , PTEN ), a 125 bp region of the TERT promoter, and 54 single nucleotide polymorphisms (SNPs) along chromosomes 1 and 19 for reliable assessment of their copy number alterations (CNAs). Our targeted NGS approach provided a portrait of gliomas' molecular heterogeneity with high accuracy, specificity, and sensitivity in a single workflow, enabling the detection of variants associated with unfavorable outcomes, disease progression, and drug resistance. These preliminary results support its use in routine diagnostic neuropathology.
Keyphrases
- copy number
- high grade
- mitochondrial dna
- low grade
- genome wide
- dna methylation
- cancer therapy
- end stage renal disease
- single cell
- small cell lung cancer
- single molecule
- newly diagnosed
- gene expression
- ejection fraction
- cell proliferation
- epidermal growth factor receptor
- metabolic syndrome
- clinical practice
- transcription factor
- peritoneal dialysis
- tyrosine kinase
- signaling pathway
- weight loss
- combination therapy
- patient reported
- label free
- sensitive detection
- cell free