title: Circulating tumour DNA reflects treatment response and clonal evolution in chronic lymphocytic leukaemia.
abstract: Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and the increasing use of these therapies has highlighted limitations of traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror the genomic information contained within circulating malignant lymphocytes but instead parallels changes across different disease compartments following treatment with novel therapies. Serial ctDNA analysis allows clonal dynamics to be monitored over time and identifies the emergence of genomic changes associated with Richter's syndrome (RS). In addition to conventional disease monitoring, ctDNA provides a unique opportunity for non-invasive serial analysis of CLL for molecular disease monitoring.
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Yeh
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Tane
authors.initials: T
authors.lastname: Hunter
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Devbarna
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ftouni
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Elise
authors.initials: E
authors.lastname: Wallach
authors.affiliation: Department of Radiology, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Damian
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Yih-Chih
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Stephen Q
authors.initials: SQ
authors.lastname: Wong
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Maria Joao
authors.initials: MJ
authors.lastname: Silva
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Ravikiran
authors.identifier: 0000-0002-8816-1807
authors.initials: R
authors.lastname: Vedururu
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Doig
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Enid
authors.initials: E
authors.lastname: Lam
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Gisela Mir
authors.initials: GM
authors.lastname: Arnau
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Semple
authors.affiliation: Victorian Cancer Cytogenetics Service, St Vincent's Hospital, Fitzroy, Victoria 3065, Australia.|Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Wall
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Andjelija
authors.initials: A
authors.lastname: Zivanovic
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: Rishu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Petrone
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Jones
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Westerman
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
authors.forename: Piers
authors.initials: P
authors.lastname: Blombery
authors.affiliation: Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.|Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3000, Australia.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.|Centre for Cancer Research, University of Melbourne, Parkville, Victoria 3000, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Dawson
authors.affiliation: Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.|Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria 3065, Australia.|Department of Haematology, St Vincent's Hospital, Fitzroy, Victoria 3065, Australia.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Tam
authors.affiliation: Division of Cancer Research, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Victoria 3000, Australia.|Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria 3000, Australia.|Centre for Cancer Research, University of Melbourne, Parkville, Victoria 3000, Australia.
authors.forename: Sarah-Jane
authors.initials: SJ
authors.lastname: Dawson
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D000075747:Baculoviral IAP Repeat-Containing 3 Protein / Q000235:genetics; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000627:therapeutic use; D000074141:Circulating Tumor DNA / Q000097:blood / Q000235:genetics*; D060965:Clonal Evolution / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D010880:Piperidines; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D000072260:RNA Splicing Factors / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000074141:Circulating Tumor DNA; C117307:KRAS protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; C112491:SF3B1 protein, human; D013449:Sulfonamides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C551803:ibrutinib; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D016283:Proto-Oncogene Proteins p21(ras); D000225:Adenine; C579720:venetoclax