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Abstract：
BACKGROUND: Primary central nervous system lymphoma (PCNSL) are rare mature B-cell lymphoproliferative diseases characterized by a high incidence of MYD88 L265P and CD79B Y196 hotspot mutations. Diagnosis of PCNSL can be challenging. The aim of the study was to analyze the detection rate of the MYD88 L265P and CD79B Y196 mutation in cell free DNA (cfDNA) in plasma of patients with PCNSL.
METHODS: We analyzed by digital droplet PCR (ddPCR) to determine presence of the MYD88 L265P and CD79B Y196 hotspot mutations in cfDNA isolated from plasma of 24 PCNSL patients with active disease. Corresponding tumor samples were available for 14 cases. Based on the false positive rate observed in 8 healthy control samples, a stringent cut-off for the MYD88 L265P and CD79B Y196 mutation were set at 0.3% and 0.5%, respectively.
RESULTS: MYD88 L265P and CD79B Y196 mutations were detected in 9/14 (64%) and 2/13 (15%) tumor biopsies, respectively. In cfDNA samples, the MYD88 L265P mutation was detected in 3/24 (12.5%), while the CD79B Y196 mutation was not detected in any of the 23 tested cfDNA samples. Overall, MYD88 L265P and/or CD79B Y196 were detected in cfDNA in 3/24 cases (12.5%). The detection rate of the combined analysis did not improve the single detection rate for either MYD88 L265P or CD79B Y196.
CONCLUSIONS: The low detection rate of MYD88 L265P and CD79B Y196 mutations in cfDNA in the plasma of PCNSL patients argues against its use in routine diagnostics. However, detection of MYD88 L265P by ddPCR in cfDNA in the plasma could be considered in challenging cases.
METHODS: We analyzed by digital droplet PCR (ddPCR) to determine presence of the MYD88 L265P and CD79B Y196 hotspot mutations in cfDNA isolated from plasma of 24 PCNSL patients with active disease. Corresponding tumor samples were available for 14 cases. Based on the false positive rate observed in 8 healthy control samples, a stringent cut-off for the MYD88 L265P and CD79B Y196 mutation were set at 0.3% and 0.5%, respectively.
RESULTS: MYD88 L265P and CD79B Y196 mutations were detected in 9/14 (64%) and 2/13 (15%) tumor biopsies, respectively. In cfDNA samples, the MYD88 L265P mutation was detected in 3/24 (12.5%), while the CD79B Y196 mutation was not detected in any of the 23 tested cfDNA samples. Overall, MYD88 L265P and/or CD79B Y196 were detected in cfDNA in 3/24 cases (12.5%). The detection rate of the combined analysis did not improve the single detection rate for either MYD88 L265P or CD79B Y196.
CONCLUSIONS: The low detection rate of MYD88 L265P and CD79B Y196 mutations in cfDNA in the plasma of PCNSL patients argues against its use in routine diagnostics. However, detection of MYD88 L265P by ddPCR in cfDNA in the plasma could be considered in challenging cases.
摘要：
背景：原发性中枢神经系统淋巴瘤（PCNSL）是罕见的成熟B细胞淋巴增殖性疾病，其特征是MYD88L265P和CD79BY196热点突变的发生率很高。PCNSL的诊断具有挑战性。该研究的目的是分析PCNSL患者血浆中无细胞DNA（cfDNA）中MYD88L265P和CD79BY196突变的检出率。
方法：我们通过数字液滴PCR（ddPCR）进行分析，以确定从24名患有活动性疾病的PCNSL患者血浆中分离的cfDNA中是否存在MYD88L265P和CD79BY196热点突变。14例患者有相应的肿瘤样本。根据在8个健康对照样本中观察到的假阳性率，MYD88L265P和CD79BY196突变的严格截断值设定为0.3%和0.5%，分别。
结果：在9/14（64％）和2/13（15％）的肿瘤活检中检测到MYD88L265P和CD79BY196突变，分别。在cfDNA样本中，在3/24（12.5％）中检测到MYD88L265P突变，而在23份检测的cfDNA样本中均未检测到CD79BY196突变。总的来说,在3/24例（12.5％）的cfDNA中检测到MYD88L265P和/或CD79BY196。组合分析的检出率没有提高MYD88L265P或CD79BY196的单一检出率。
结论：PCNSL患者血浆cfDNA中MYD88L265P和CD79BY196突变的低检出率证明了其在常规诊断中的应用。然而,在具有挑战性的病例中，可以考虑通过ddPCR在血浆中cfDNA中检测MYD88L265P。
方法：我们通过数字液滴PCR（ddPCR）进行分析，以确定从24名患有活动性疾病的PCNSL患者血浆中分离的cfDNA中是否存在MYD88L265P和CD79BY196热点突变。14例患者有相应的肿瘤样本。根据在8个健康对照样本中观察到的假阳性率，MYD88L265P和CD79BY196突变的严格截断值设定为0.3%和0.5%，分别。
结果：在9/14（64％）和2/13（15％）的肿瘤活检中检测到MYD88L265P和CD79BY196突变，分别。在cfDNA样本中，在3/24（12.5％）中检测到MYD88L265P突变，而在23份检测的cfDNA样本中均未检测到CD79BY196突变。总的来说,在3/24例（12.5％）的cfDNA中检测到MYD88L265P和/或CD79BY196。组合分析的检出率没有提高MYD88L265P或CD79BY196的单一检出率。
结论：PCNSL患者血浆cfDNA中MYD88L265P和CD79BY196突变的低检出率证明了其在常规诊断中的应用。然而,在具有挑战性的病例中，可以考虑通过ddPCR在血浆中cfDNA中检测MYD88L265P。
