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ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid

Backgrounds & Purpose: Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumor. Brain biopsy is indispensable to confirm the diagnosis of CNSL, but has a potential risk of inducing hemorrhagic complications in the brain. Therefore, liquid biopsy using the c...

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Autores principales: Yamagishi, Yuki, Sasaki, Nobuyoshi, Matsushita, Yuko, Shimizu, Saki, Saito, Kuniaki, Kobayashi, Keiichi, Shiokawa, Yoshiaki, Nagane, Motoo, Ichimura, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699077/
http://dx.doi.org/10.1093/noajnl/vdaa143.069
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author Yamagishi, Yuki
Sasaki, Nobuyoshi
Matsushita, Yuko
Shimizu, Saki
Saito, Kuniaki
Kobayashi, Keiichi
Shiokawa, Yoshiaki
Nagane, Motoo
Ichimura, Koichi
author_facet Yamagishi, Yuki
Sasaki, Nobuyoshi
Matsushita, Yuko
Shimizu, Saki
Saito, Kuniaki
Kobayashi, Keiichi
Shiokawa, Yoshiaki
Nagane, Motoo
Ichimura, Koichi
author_sort Yamagishi, Yuki
collection PubMed
description Backgrounds & Purpose: Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumor. Brain biopsy is indispensable to confirm the diagnosis of CNSL, but has a potential risk of inducing hemorrhagic complications in the brain. Therefore, liquid biopsy using the cerebrospinal fluid (CSF) has attracted an attention as a less invasive diagnostic method. In this study, we established a digital PCR-based method to detect MYD88 mutations in CSF and evaluated its efficacy. Methods: Matched CSF and biopsy samples from CNSL patients collected before the start of chemotherapy were used. Cellular DNA and cell free DNA (cfDNA) of CSF were separately extracted from the pellet and the supernatant fraction of CSF, respectively. Presence of the MYD88 L265P mutation was examined in each fraction by the digital PCR. The mutational status obtained by liquid biopsy was compared with that of the matched biopsy specimen examined by pyrosequencing. Result: A total of 36 paired samples were used. When the cutoff value of Target/Total ratio was 0.25%, sensitivity, specificity, and area under the curve (AUC) of the digital PCR detection using cellular DNA were 92.9%, 100%, and 0.95, respectively, while they were 100%, 100%, and 1.00 using cfDNA. Conclusion: We showed that the digital PCR method was highly sensitive and specific in detecting MYD88 mutations in the CSF. We propose that CSF liquid biopsy may serve a clinically applicable surrogate to make a diagnosis of CNSL.
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spelling pubmed-76990772020-12-02 ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid Yamagishi, Yuki Sasaki, Nobuyoshi Matsushita, Yuko Shimizu, Saki Saito, Kuniaki Kobayashi, Keiichi Shiokawa, Yoshiaki Nagane, Motoo Ichimura, Koichi Neurooncol Adv Supplement Abstracts Backgrounds & Purpose: Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumor. Brain biopsy is indispensable to confirm the diagnosis of CNSL, but has a potential risk of inducing hemorrhagic complications in the brain. Therefore, liquid biopsy using the cerebrospinal fluid (CSF) has attracted an attention as a less invasive diagnostic method. In this study, we established a digital PCR-based method to detect MYD88 mutations in CSF and evaluated its efficacy. Methods: Matched CSF and biopsy samples from CNSL patients collected before the start of chemotherapy were used. Cellular DNA and cell free DNA (cfDNA) of CSF were separately extracted from the pellet and the supernatant fraction of CSF, respectively. Presence of the MYD88 L265P mutation was examined in each fraction by the digital PCR. The mutational status obtained by liquid biopsy was compared with that of the matched biopsy specimen examined by pyrosequencing. Result: A total of 36 paired samples were used. When the cutoff value of Target/Total ratio was 0.25%, sensitivity, specificity, and area under the curve (AUC) of the digital PCR detection using cellular DNA were 92.9%, 100%, and 0.95, respectively, while they were 100%, 100%, and 1.00 using cfDNA. Conclusion: We showed that the digital PCR method was highly sensitive and specific in detecting MYD88 mutations in the CSF. We propose that CSF liquid biopsy may serve a clinically applicable surrogate to make a diagnosis of CNSL. Oxford University Press 2020-11-28 /pmc/articles/PMC7699077/ http://dx.doi.org/10.1093/noajnl/vdaa143.069 Text en © The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Supplement Abstracts
Yamagishi, Yuki
Sasaki, Nobuyoshi
Matsushita, Yuko
Shimizu, Saki
Saito, Kuniaki
Kobayashi, Keiichi
Shiokawa, Yoshiaki
Nagane, Motoo
Ichimura, Koichi
ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title_full ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title_fullStr ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title_full_unstemmed ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title_short ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
title_sort ml-06 diagnostic value of liquid biopsy for cns lymphoma by detection of specific gene mutations in the cerebrospinal fluid
topic Supplement Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699077/
http://dx.doi.org/10.1093/noajnl/vdaa143.069
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