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Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma
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Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma
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Journal Article
Liquid biopsy of cerebrospinal fluid for MYD88 L265P mutation is useful for diagnosis of central nervous system lymphoma
2021
Overview
The current standard of diagnosing central nervous system (CNS) lymphoma is stereotactic biopsy, however the procedure has a risk of surgical complication. Liquid biopsy of the CSF is a less invasive, non‐surgical method that can be used for diagnosing CNS lymphoma. In this study, we established a clinically applicable protocol for determining mutations in MYD88 in the CSF of patients with CNS lymphoma. CSF was collected prior to the start of chemotherapy from 42 patients with CNS lymphoma and matched tumor specimens. Mutations in MYD88 in 33 tumor samples were identified using pyrosequencing. Using 10 ng each of cellular DNA and cell‐free DNA (cfDNA) extracted from the CSF, the MYD88 L265P mutation was detected using digital PCR. The conditions to judge mutation were rigorously determined. The median Target/Total value of cases with MYD88 mutations in the tumors was 5.1% in cellular DNA and 22.0% in cfDNA. The criteria to judge mutation were then determined, with a Target/Total value of 0.25% as the cutoff. When MYD88 mutations were determined based on these criteria, the sensitivity and specificity were 92.2% and 100%, respectively, with cellular DNA; and the sensitivity and specificity were 100% with cfDNA. Therefore, the DNA yield, mutated allele fraction, and accuracy were significantly higher in cfDNA compared with that in cellular DNA. Taken together, this study highlights the importance of detecting the MYD88 L265P mutation in cfDNA of the CSF for diagnosing CNS lymphoma using digital PCR, a highly accurate and clinically applicable method. Development of a liquid biopsy for less invasive diagnosis of CNS lymphoma is in progress. In this study, the conditions for detecting the MYD88 L265P mutation by digital PCR were set, and extremely high accuracy was confirmed. This method is fully clinically feasible.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Aged
/ Biopsy
/ Cell-Free Nucleic Acids - cerebrospinal fluid
/ Cell-Free Nucleic Acids - genetics
/ Cell-Free Nucleic Acids - isolation & purification
/ central nervous system lymphoma
/ Central Nervous System Neoplasms - cerebrospinal fluid
/ Central Nervous System Neoplasms - diagnosis
/ Central Nervous System Neoplasms - genetics
/ DNA
/ DNA, Neoplasm - cerebrospinal fluid
/ DNA, Neoplasm - isolation & purification
/ Female
/ High-Throughput Nucleotide Sequencing - methods
/ Humans
/ Lymphoma
/ Lymphoma - cerebrospinal fluid
/ Male
/ Mutation
/ MYD88
/ Myeloid Differentiation Factor 88 - cerebrospinal fluid
/ Myeloid Differentiation Factor 88 - genetics
/ Original
/ Patients
/ Polymerase Chain Reaction - methods
/ Tumors
