Liquid Biopsy for CNS Lymphoma
(2021)Objective
To evaluate the diagnostic accuracy of digital PCR-based detection of MYD88 L265P mutation in CSF for CNS lymphoma.
Study Summary
• MYD88 mutation detected in 100% of CNS lymphoma cases using CSF cfDNA
• Sensitivity and specificity reached 100% with optimized digital PCR
• Mutation detection matched 100% with tumor tissue genotyping
• Sensitivity and specificity reached 100% with optimized digital PCR
• Mutation detection matched 100% with tumor tissue genotyping
Intervention
Digital PCR was performed on CSF from 42 patients with CNS lymphoma to detect MYD88 L265P mutations. CSF was collected before treatment, and both cellular and cell-free DNA were extracted. Matched tumor samples were used for confirmation. Mutation detection thresholds and quality metrics were rigorously optimized.
Inclusion Criteria
Patients with histologically confirmed CNS lymphoma and available CSF and tumor tissue samples.
Study Design
Arms: Single-arm observational
Patients per Arm: 42
Outcome
• MYD88 L265P mutation found in 78.6% (33/42) of tumor tissues by pyrosequencing
• Digital PCR of CSF cfDNA detected mutation in 100% of positive cases
• Sensitivity and specificity were 100% using cfDNA; 92.2% and 100% using cellular DNA
• Median mutant allele fraction: 17.9% in cfDNA vs. 5.1% in cellular DNA
• A single patient case confirmed diagnosis solely through CSF biopsy when brain biopsy was not feasible
• Digital PCR of CSF cfDNA detected mutation in 100% of positive cases
• Sensitivity and specificity were 100% using cfDNA; 92.2% and 100% using cellular DNA
• Median mutant allele fraction: 17.9% in cfDNA vs. 5.1% in cellular DNA
• A single patient case confirmed diagnosis solely through CSF biopsy when brain biopsy was not feasible