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Bone marrow involvement and subclonal diversity impairs detection of mutated CXCR4 by diagnostic next‐generation sequencing in Waldenström macroglobulinaemia
Author(s) -
Gustine Joshua N.,
Xu Lian,
Yang Guang,
Liu Xia,
Kofides Amanda,
Tsakmaklis Nicholas,
Munshi Manit,
Demos Maria,
Guerrera Maria L.,
Meid Kirsten,
Patterson Christopher J.,
Sarosiek Shayna,
Branagan Andrew R.,
Hunter Zachary R.,
Castillo Jorge J.,
Treon Steven P.
Publication year - 2021
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.17385
Subject(s) - sanger sequencing , bone marrow , cxcr4 , medicine , dna sequencing , waldenstrom macroglobulinemia , polymerase chain reaction , oncology , biology , immunology , genetics , gene , lymphoma , chemokine , immune system
Summary CXCR4 mutations impact disease presentation and treatment outcomes in Waldenström macroglobulinaemia (WM). Non‐uniform testing for CXCR4 mutations may account for discordant findings in WM clinical trials. We compared two approaches used in these trials for detection of the most common CXCR4 (S338X) variant: targeted next‐generation sequencing (NGS) using unselected bone marrow (BM) samples, and combined allele‐specific polymerase chain reaction (AS‐PCR) and Sanger sequencing with unselected and CD19‐selected BM samples. Our findings showed that targeted NGS frequently yielded false‐negative results. Both CD19 selection and AS‐PCR markedly improved detection of CXCR4 S338X mutations. Sensitivity was adversely impacted by low BM involvement and CXCR4 mutation clonality.