Analysis of driver mutational hot spots in blood-derived cell-free DNA of patients with primary central nervous system lymphoma obtained before intracerebral biopsy

Item Type:	Article
Title:	Analysis of driver mutational hot spots in blood-derived cell-free DNA of patients with primary central nervous system lymphoma obtained before intracerebral biopsy
Creators Name:	Montesinos-Rongen, M. and Brunn, A. and Tuchscherer, A. and Borchmann, P. and Schorb, E. and Kasenda, B. and Altmüller, J. and Illerhaus, G. and Ruge, M.I. and Maarouf, M. and Büttner, R. and Hansmann, M.L. and Hallek, M. and Prinz, M. and Siebert, R. and Deckert, M.
Abstract:	In newly diagnosed systemic diffuse large B-cell lymphoma, next-generation sequencing of plasma-derived cell-free DNA (cfDNA) detects somatic mutations as accurate as genotyping of the tumor biopsy. A distinct diffuse large B-cell lymphoma entity confined to the central nervous system is primary central nervous system lymphoma (PCNSL), which requires intracerebral biopsy and neuropathologic analysis to establish the diagnosis. So far, a biomarker for diagnosis and follow-up of PCNSL that can be investigated in blood has not been identified. This article addresses the question whether somatic mutations of the CD79B and MYD88 driver genes of PCNSL can be detected in cfDNA at disease diagnosis. Stereotactic biopsies and cfDNA of 27 PCNSL patients were analyzed for CD79B and MYD88 mutations. As control, cfDNA derived from six healthy volunteers was used. CD79B and MYD88 hot spot mutations were identified in 16 of 27 (59%) and 23 of 27 (85%) PCNSL biopsies, respectively, but only in 0 of 27 (0%) and 1 of 27 (4%) corresponding cfDNA samples, respectively. In cfDNA of one of four patients with Waldenstrom disease, as a further control, the MYD88 L265P mutation was readily detected, despite complete clinical remission. These data suggest that in PCNSL even if they carry such mutations, alterations of CD79B and MYD88 cannot be reliably detected in blood-derived cfDNA obtained before intracerebral biopsy.
Keywords:	Biopsy, Brain, CD79 Antigens, Cell-Free Nucleic Acids, Central Nervous System Neoplasms, Gene Frequency, High-Throughput Nucleotide Sequencing, Lymphoma, Mutation, Myeloid Differentiation Factor 88
Source:	Journal of Molecular Diagnostics
ISSN:	1525-1578
Publisher:	Elsevier
Volume:	22
Number:	10
Page Range:	1300-1307
Date:	October 2020
Official Publication:	https://doi.org/10.1016/j.jmoldx.2020.07.002
PubMed:	View item in PubMed

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