Utility of targeted next-generation sequencing assay to detect 1p/19q co-deletion in formalin- fixed paraffin-embedded glioma specimens

Molecular classification of brain neoplasms is important for diagnosis, prognosis, and treatment outcome of histologically similar tumors. Oligodendroglioma is a glioma subtype characterized by 1p/19q co-deletion and IDH1/IDH2 mutations, which predict a good prognosis, responsiveness to therapy, and an improved overall survival compared to other adult gliomas. In a routine clinical setting, 1p/19q co-deletion is detected by interphase-FISH and SNP microarray, and somatic mutations are detected by targeted next-generation sequencing (NGS). The aim of this proof-of-principle study was to investigate the feasibility of using targeted NGS to simultaneously detect both 1p/19q co-deletion and somatic mutations. Among 247 consecutive patients with formalin-fixed paraffin-embedded brain tumors with various subtypes, NGS revealed 1p/19q co-deletion in 26 oligodendrogliomas and an IDH-wildtype astrocytoma, and partial loss across chromosomes 1p and 19q/whole-arm loss of 1p or 19q/copy neutral loss of heterozygosity in 11 nonoligodendrogliom as. For this 247 brain-tumor cohort, the overall sensitivity, specificity, and accuracy of detecting 1p/19q co-deletion by NGS in oli-godendrogliomas were 96.2%, 99.6%, and 99.2%, respectively. The oligodendroglioma cohort hadmore mutations inI DH1/IDH2,CIC,FUBP1, and TERT, and fewer mutations inATRXandTP53thanthe nonoligodendroglioma cohort. This proof-of-concept study demonstrated that targeted NGS can simultaneously detect both 1p/19q co-deletion and somatic mutations, which can provide a more comprehensive genetic profiling for patients with gliomas using a single assay in a clinical setting. (C) 2022 Published by Elsevier Inc.

Automated summary

Molecular classification of brain neoplasms is crucial for diagnosis, prognosis, and treatment outcomes. This proof-of-concept study demonstrated the feasibility of using targeted next-generation sequencing (NGS) to simultaneously detect 1p/19q co-deletion and somatic mutations, providing a more comprehensive genetic profiling for glioma patients.