A rapid genotyping panel for detection of primary central nervous system lymphoma
A rapid genotyping panel for detection of primary central nervous system lymphoma
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DOI：
10.1182/blood.2020010137
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发表时间：
2021-08-05
期刊：
影响因子：
20.3
通讯作者：
Shankar, Ganesh M.
中科院分区：
文献类型：
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作者：
Gupta, Mihir;Burns, Evan J.;Shankar, Ganesh M.
原发性中枢神经系统淋巴瘤(PCNSL)的诊断通常需要神经外科活检，因为没有特殊的放射学特征，而且脑脊液(CSF)检查的效率很低。我们对可疑的PCNSL患者(N=1007例)进行了临床评估，并设计了一种MYD88、TERT启动子、IDH1/2、H3F3A和BRAF突变的快速多重基因分型方法，以便于从脑脊液中诊断PCNSL并在鉴别诊断中检测其他肿瘤。在159名确诊为PCNSL的患者中，确诊PCNSL的中位时间为10天，范围为0至617天。永久性组织病理学证实152例活检中有142例(93.4%)确诊为PCNSL，而脑脊液分析只有15/113例(13.3%)确诊。在86份存档的临床标本中，我们的靶向基因分型方法准确地检测出恶性血液病的敏感度和特异度分别为57.6%和100%(95%可信区间[CI]：44.1%~70.4%和87.2%~100%)。在80分钟内分别从PCNSL和胶质母细胞瘤患者的脑脊液DNA提取液中发现MyD88和TERT启动子突变。在132个样本中，检测到指示存在恶性肿瘤的标志性突变的敏感性和特异性分别为65.8%和100%(95%CI：56.2%~74.5%和83.9%~100%)。这种有针对性的基因分型方法提供了一种快速、可扩展的辅助手段，以减少PCNSL的诊断和治疗延迟。
Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified inDNA extracts of CSF obtained frompatientswith PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.