- J Neuropathol Exp Neurol（Shiba、Aoki、Saito 等，名古屋大学）：2019 年 3 月—2025 年 1 月连续 307 例弥漫性胶质瘤，回顾性评估以 Sanger 测序 + MLPA 为核心的靶向分子流程。
- 288/307（93.8%）确立 WHO 2021 整合诊断，仅 19 例（6.2%）未能明确。
- 分子结果改变了 60 例（19.5%）的组织学诊断：最常见为分子胶质母细胞瘤、H3K27 改变型、1p/19q 全臂共缺失少突、CDKN2A/B 纯合缺失升为 4 级的星形细胞瘤，以及 H3 G34 突变型弥漫性半球胶质瘤。
- 实践提示：在无法常规做全面基因组测序的科室，Sanger + MLPA 可覆盖大多数整合诊断，只有少数病例需进一步检测。本站仅获摘要。
收录范围：PubMed 摘要中英对照。原文为 OUP 订阅内容，本站未获全文与图表。
摘要
2021 年世界卫生组织（WHO）中枢神经系统肿瘤分类要求以分子改变作出弥漫性胶质瘤的整合诊断，但常规工作中是否必须进行全面基因组分析仍不确定。我们回顾性评估了一套以 Sanger 测序和多重连接依赖探针扩增（MLPA）为基础的实用分子诊断流程，对象为 2019 年 3 月至 2025 年 1 月间连续诊断的 307 例弥漫性胶质瘤。组织病理诊断由 2 名具备专科资质的神经病理医师独立作出，并与最终的 WHO 2021 整合诊断进行比较。靶向分子检测检出了具有诊断意义的突变和拷贝数改变。307 例中有 288 例（93.8%）确立了整合诊断，仅 19 例（6.2%）未能明确。分子结果改变了 60 例（19.5%）的组织病理诊断，247 例（80.5%）的组织病理诊断与整合诊断一致。重新分类最常见的情形为：分子胶质母细胞瘤、H3K27 改变型弥漫性胶质瘤、以 1p/19q 全臂共缺失定义的少突胶质细胞瘤、因 CDKN2A/B 纯合性缺失升为 WHO 4 级的星形细胞瘤，以及弥漫性半球胶质瘤，H3 G34 突变型。结果表明，Sanger 测序与 MLPA 相结合的流程可为大多数弥漫性胶质瘤确立 WHO 2021 整合诊断提供实用途径，仅一小部分病例需要进一步分子检测。
- J Neuropathol Exp Neurol (Shiba, Aoki, Saito and colleagues, Nagoya University): a retrospective evaluation of a targeted Sanger sequencing plus MLPA workflow in 307 consecutive diffuse gliomas (March 2019 to January 2025).
- Integrated WHO 2021 diagnoses were established in 288/307 (93.8%); only 19 (6.2%) remained unresolved.
- Molecular findings changed the histological diagnosis in 60 (19.5%), most often molecular glioblastoma, H3K27-altered glioma, 1p/19q-codeleted oligodendroglioma, CDKN2A/B-deleted grade 4 astrocytoma and H3 G34-mutant diffuse hemispheric glioma.
- Practice point: where comprehensive genomic profiling is not routine, Sanger plus MLPA resolves most integrated diagnoses, with only a small subset needing more testing. Abstract only.
Scope: the PubMed abstract. The article is subscription content at OUP; the full text and figures were not obtained.
Abstract
The 2021 World Health Organization (WHO) Classification of Tumors of the Central Nervous System requires molecular alterations for the integrated diagnosis of diffuse gliomas but the necessity of comprehensive genomic profiling in routine practice remains uncertain. We retrospectively evaluated a practical molecular diagnostic workflow using Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) in 307 consecutive diffuse gliomas diagnosed between March 2019 and January 2025. Histopathological diagnoses were established independently by 2 board-certified neuropathologists and compared with the final WHO 2021 integrated diagnoses. Targeted molecular testing identified diagnostically relevant mutations and copy-number alterations. Integrated diagnoses were established in 288 of 307 tumors (93.8%), leaving only 19 cases (6.2%) unresolved. Molecular findings changed the histopathological diagnosis in 60 tumors (19.5%), whereas 247 tumors (80.5%) showed concordant histopathological and integrated diagnoses. Reclassification most frequently involved molecular glioblastoma, H3K27-altered diffuse glioma, oligodendroglioma defined by whole-arm 1p/19q codeletion, astrocytoma upgraded to WHO grade 4 based on CDKN2A/B homozygous deletion, and diffuse hemispheric glioma, H3 G34-mutant. These results demonstrate that a workflow combining Sanger sequencing and MLPA provides a practical approach for establishing WHO 2021 integrated diagnoses in most diffuse gliomas, with only a small subset requiring additional molecular characterization.