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


  • M. Montesinos-Rongen
  • A. Brunn
  • A. Tuchscherer
  • P. Borchmann
  • E. Schorb
  • B. Kasenda
  • J. Altmüller
  • G. Illerhaus
  • M.I. Ruge
  • M. Maarouf
  • R. Büttner
  • M.L. Hansmann
  • M. Hallek
  • M. Prinz
  • R. Siebert
  • M. Deckert


  • Journal of Molecular Diagnostics


  • J Mol Diagn 22 (10): 1300-1307


  • 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.