Open AccessClinical significance of disease‐specific MYD 88 mutations in circulating DNA in primary central nervous system lymphoma
Author(s) -
Hattori Keiichiro,
SakataYanagimoto Mamiko,
Suehara Yasuhito,
Yokoyama Yasuhisa,
Kato Takayasu,
Kurita Naoki,
Nishikii Hidekazu,
Obara Naoshi,
Takano Shingo,
Ishikawa Eiichi,
Matsumura Akira,
Hasegawa Yuichi,
Chiba Shigeru
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13450
Subject(s) - mutation , dna , lymphoma , minimal residual disease , digital polymerase chain reaction , primary central nervous system lymphoma , dna sequencing , cancer research , biology , chemotherapy , polymerase chain reaction , microbiology and biotechnology , gene , genetics , immunology , leukemia
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 .