title: Molecular disease monitoring using circulating tumor DNA in myelodysplastic syndromes.
abstract: The diagnosis and monitoring of myelodysplastic syndromes (MDSs) are highly reliant on bone marrow morphology, which is associated with substantial interobserver variability. Although azacitidine is the mainstay of treatment in MDS, only half of all patients respond. Therefore, there is an urgent need for improved modalities for the diagnosis and monitoring of MDSs. The majority of MDS patients have either clonal somatic karyotypic abnormalities and/or gene mutations that aid in the diagnosis and can be used to monitor treatment response. Circulating cell-free DNA is primarily derived from hematopoietic cells, and we surmised that the malignant MDS genome would be a major contributor to cell-free DNA levels in MDS patients as a result of ineffective hematopoiesis. Through analysis of serial bone marrow and matched plasma samples (n = 75), we demonstrate that cell-free circulating tumor DNA (ctDNA) is directly comparable to bone marrow biopsy in representing the genomic heterogeneity of malignant clones in MDS. Remarkably, we demonstrate that serial monitoring of ctDNA allows concurrent tracking of both mutations and karyotypic abnormalities throughout therapy and is able to anticipate treatment failure. These data highlight the role of ctDNA as a minimally invasive molecular disease monitoring strategy in MDS.
authors.affiliation: Division of Cancer Research, and.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.|Sir Peter MacCallum Department of Oncology, and.
authors.forename: Paul
authors.initials: P
authors.lastname: Yeh
authors.affiliation: Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Dickinson
authors.affiliation: Division of Cancer Research, and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ftouni
authors.affiliation: Division of Cancer Research, and.|Sir Peter MacCallum Department of Oncology, and.
authors.forename: Tane
authors.initials: T
authors.lastname: Hunter
authors.affiliation: Division of Cancer Research, and.
authors.forename: Devbarna
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Division of Cancer Research, and.
authors.forename: Stephen Q
authors.initials: SQ
authors.lastname: Wong
authors.affiliation: Division of Cancer Research, and.|Sir Peter MacCallum Department of Oncology, and.
authors.forename: Rishu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Division of Cancer Research, and.
authors.forename: Ravikiran
authors.initials: R
authors.lastname: Vedururu
authors.affiliation: Division of Cancer Research, and.|Sir Peter MacCallum Department of Oncology, and.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Doig
authors.affiliation: Division of Cancer Research, and.|Sir Peter MacCallum Department of Oncology, and.
authors.forename: Chun Yew
authors.initials: CY
authors.lastname: Fong
authors.affiliation: Division of Cancer Research, and.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.
authors.forename: Piers
authors.initials: P
authors.lastname: Blombery
authors.affiliation: Division of Cancer Research, and.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.
authors.forename: David
authors.initials: D
authors.lastname: Westerman
authors.affiliation: Division of Cancer Research, and.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.|Sir Peter MacCallum Department of Oncology, and.|Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Mark A
authors.identifier: 0000-0002-5464-5029
authors.initials: MA
authors.lastname: Dawson
authors.affiliation: Division of Cancer Research, and.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; and.|Sir Peter MacCallum Department of Oncology, and.|Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Sarah-Jane
authors.identifier: 0000-0002-8276-0374
authors.initials: SJ
authors.lastname: Dawson
mesh_terms: D001374:Azacitidine / Q000627:therapeutic use; D001856:Bone Marrow Examination; D002999:Clone Cells / Q000473:pathology; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D007621:Karyotyping; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D001374:Azacitidine