Johns Hopkins Genomics, USA; Department of Pathology, Johns Hopkins University School of Medicine, USA.
Johns Hopkins Genomics, USA; Department of Pathology, Johns Hopkins University School of Medicine, USA; Cytogenetics Laboratory, Johns Hopkins University Hospital, Baltimore, MD, 21205, USA.
Hum Pathol. 2022 Aug;126:63-76. doi: 10.1016/j.humpath.2022.05.001. Epub 2022 May 10.
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 nonoligodendrogliomas. For this 247 brain-tumor cohort, the overall sensitivity, specificity, and accuracy of detecting 1p/19q co-deletion by NGS in oligodendrogliomas were 96.2%, 99.6%, and 99.2%, respectively. The oligodendroglioma cohort had more mutations in IDH1/IDH2, CIC, FUBP1, and TERT, and fewer mutations in ATRX and TP53 than the 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.
脑肿瘤的分子分类对于组织学相似肿瘤的诊断、预后和治疗结果非常重要。少突胶质细胞瘤是一种胶质瘤亚型，其特征是 1p/19q 共缺失和 IDH1/IDH2 突变，与其他成人胶质瘤相比，其预后较好，对治疗有反应，总生存期得到改善。在常规临床环境中，通过间期-FISH 和 SNP 微阵列检测 1p/19q 共缺失，通过靶向下一代测序（NGS）检测体细胞突变。本原理验证研究的目的是研究使用靶向 NGS 同时检测 1p/19q 共缺失和体细胞突变的可行性。在 247 例福尔马林固定石蜡包埋的具有各种亚型的脑肿瘤连续患者中，NGS 显示 26 例少突胶质细胞瘤和 1 例 IDH 野生型星形细胞瘤存在 1p/19q 共缺失，11 例非少突胶质细胞瘤中存在 1p 染色体部分缺失和 19q/1p 整条缺失或杂合性缺失。对于这 247 例脑肿瘤队列，NGS 检测少突胶质细胞瘤中 1p/19q 共缺失的总敏感性、特异性和准确性分别为 96.2%、99.6%和 99.2%。与非少突胶质细胞瘤队列相比，少突胶质细胞瘤队列中 IDH1/IDH2、CIC、FUBP1 和 TERT 的突变更多，而 ATRX 和 TP53 的突变更少。本概念验证研究表明，靶向 NGS 可以同时检测 1p/19q 共缺失和体细胞突变，使用单个检测可以为胶质瘤患者提供更全面的遗传分析。
