
Mutations found in cell‐free DNA s of patients with malignant lymphoma at remission can derive from clonal hematopoiesis
Author(s) -
Suehara Yasuhito,
SakataYanagimoto Mamiko,
Hattori Keiichiro,
Kusakabe Manabu,
Nanmoku Toru,
Sato Taiki,
Noguchi Masayuki,
Chiba Shigeru
Publication year - 2019
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.14176
Subject(s) - lymphoma , cancer research , biology , carcinogenesis , mutation , haematopoiesis , microbiology and biotechnology , gene , bone marrow , dna , peripheral blood mononuclear cell , genetics , immunology , stem cell , in vitro
Cell‐free DNA (cf DNA ) analysis to detect circulating tumor DNA has been focused on monitoring malignant lymphomas. However, clonal hematopoiesis of indeterminate potential ( CHIP )‐associated mutations can also be detected by cf DNA analysis. Our aim is to investigate the origin of mutations detected in cf DNA among B‐cell lymphoma patients. MYD 88 / CD 79B , DNMT 3A , and TP 53 were chosen as genes of interest, representing each of the following categories: lymphoma driver genes, CHIP ‐related genes, and genes shared between lymphoma and CHIP . Seventy‐five B‐cell lymphoma patients were included in this retrospective study. Serum cf DNA s at time of complete metabolic response ( CMR ) were sequenced for TP 53 (N = 75) and DNMT 3A (N = 49). MYD 88 p.L265P and CD 79B p.Y196C/H mutations were analyzed in diffuse large B‐cell lymphoma ( DLBCL ) patients whose tumor samples were available (N = 29). Two and seven mutations in TP 53 and DNMT 3A , respectively, were detected in cf DNA at CMR . These mutations were detected in either bone marrow mononuclear cells ( BMMC ) or PBMC . Although four DNMT 3A mutations were also detected in tumors, median variant allele frequencies in the tumors (<1.0%) were significantly lower than those in both BMMC (6.1%) and serum (5.2%) obtained before the therapy. Conversely, five MYD 88 and three CD 79B mutations detected in tumors were confirmed in cf DNA before therapy, but not in BMMC nor in cf DNA at CMR . Thus, all TP 53 and DNMT 3A mutations detected in cf DNA at remission seemed to originate from CHIP rather than from residual disease. Results of liquid biopsy should be carefully interpreted, especially in genes shared between lymphomas and CHIP .