Open AccessUtility of plasma cell-free DNA for <i>de novo</i> detection and quantification of clonal hematopoiesis
Author(s) -
Fernanda Gutierrez-Rodrigues,
Isabel Beerman,
Emma M. Groarke,
Bhavisha Patel,
Nina Spitofsky,
Laura W. Dillon,
Diego Quis Raffo,
Christopher S. Hourigan,
Sachiko Kajigaya,
Luigi Ferrucci,
Neal S. Young
Publication year - 2021
Publication title -
haematologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.782
H-Index - 142
eISSN - 1592-8721
pISSN - 0390-6078
DOI - 10.3324/haematol.2021.279230
Subject(s) - international prognostic scoring system , aplastic anemia , haematopoiesis , myelodysplastic syndromes , hematology , bone marrow , cell free fetal dna , somatic evolution in cancer , somatic cell , immunology , allele frequency , concordance , blood cell , biology , anemia , medicine , oncology , allele , gene , cancer , genetics , stem cell , pregnancy , fetus , prenatal diagnosis
Although cell-free DNA (cfDNA) tests have emerged as a potential non-invasive alterative for bone marrow biopsies in monitoring of clonal hematopoiesis (CH) in hematologic diseases, whether commercial cfDNA assays can be implemented for de novo CH detection and quantification in place of blood cells is uncertain. In this study, peripheral plasma cfDNA samples available from patients with aplastic anemia (AA; n=25), myelodysplastic syndrome (MDS; n=27) and a healthy cohort (n=107) were screened for somatic variants in genes related to hematologic malignancies using a Clinical Laboratory Improvement Amendments-certified panel. Results were further compared to DNA sequencing of matched blood cells. In reported results, 85% of healthy subjects, 36% of AA patients and 74% of MDS patients were found to have somatic cfDNA variants, most frequently in DNMT3A, TET2, ASXL1 and SF3B1. However, concordance between cfDNA and blood cells was poor for CH detection when variants were at variant allele frequency