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Recent sequencing studies demonstrated the   MYD 88  L265P mutation in more than 70% of primary central nervous system lymphomas ( PCNSL ), and the clinical significance of this mutation has been proposed as diagnostic and prognostic markers in  PCNSL . In contrast, mutational analyses using cell‐free  DNA s have been reported in a variety of systemic lymphomas. To investigate how sensitively the   MYD 88  L265P mutation can be identified in cell‐free  DNA  from  PCNSL  patients, we carried out droplet digital  PCR  (dd PCR ) and targeted deep sequencing ( TDS ) in 14 consecutive  PCNSL  patients from whom paired tumor‐derived  DNA  and cell‐free  DNA  was available at diagnosis. The   MYD 88  L265P mutation was found in tumor‐derived  DNA  from all 14 patients (14/14, 100%). In contrast, among 14 cell‐free  DNA s evaluated by dd PCR  (14/14) and  TDS  (13/14), the   MYD 88  L265P mutation was detected in eight out of 14 (dd PCR ) and in 0 out of 13 ( TDS ) samples, implying dependence on the detection method. After chemotherapy, the   MYD 88  L265P mutation in cell‐free  DNA s was traced in five patients; unexpectedly, the mutations disappeared after chemotherapy was given, and they remained undetectable in all patients. These observations suggest that dd PCR  can sensitively detect the   MYD 88  L265P mutation in cell‐free  DNA  and could be used as non‐invasive diagnostics, but may not be applicable for monitoring minimal residual diseases in  PCNSL .

Clinical significance of disease‐specific MYD 88 mutations in circulating DNA in primary central nervous system lymphoma