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. 2024 Apr 2;24(1):407.
doi: 10.1186/s12885-024-12191-z.

Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR

Yujie Zhong  1   2 , Geok Wee Tan  2   3 , Johanna Bult  1 , Nick Veltmaat  1 , Wouter Plattel  1 , Joost Kluiver  2 , Roelien Enting  4 , Arjan Diepstra  2 , Anke van den Berg  2 , Marcel Nijland  5
Affiliations

Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR

Yujie Zhong et al. BMC Cancer. .

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.

Conclusion: 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.

Keywords: CD79B; Circulating tumor DNA; Liquid biopsy; MYD88; Primary central nervous system lymphoma.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Variant alle frequency (VAF) of MYD88 L265P and CD79B Y196 variants in. (A) In patients the VAF of MYD88 L265P ranged from 0–1% and in controls it ranged from 0–0.20%. Cut-off value was set as 0.3%. (B) In patients the VAF of CD79B Y196 ranged from 0–0.22% and in controls it ranged from 0–0.36%. Cut-off value was set as 0.5%. X-axis shows types of FFPE tissue, being controls or PCNSL. PCNSL cases are divided based on the MYD88 or CD79B ddPCR results of the tissue samples as positive, negative, or data not available (NA). Dot sizes indicate the actual total filled droplets (mutation+/wildtype+) of each cfDNA sample, ranging from 258 to 5765 filled droplets. There are 5 samples with a total number of filled droplets < 500 which were defined as inconclusive (Table S3)
Fig. 2
Fig. 2
Digital droplet PCR results of MYD88 L265P and CD79B Y196 in patients with primary CNS lymphoma
See this image and copyright information in PMC

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