ctDNA monitoring using patient-specific sequencing and integration of variant reads

Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be...

Full description

Saved in:

Bibliographic Details
Published in:	Science translational medicine Vol. 12; no. 548
Main Authors:	Wan, Jonathan C M, Heider, Katrin, Gale, Davina, Murphy, Suzanne, Fisher, Eyal, Mouliere, Florent, Ruiz-Valdepenas, Andrea, Santonja, Angela, Morris, James, Chandrananda, Dineika, Marshall, Andrea, Gill, Andrew B, Chan, Pui Ying, Barker, Emily, Young, Gemma, Cooper, Wendy N, Hudecova, Irena, Marass, Francesco, Mair, Richard, Brindle, Kevin M, Stewart, Grant D, Abraham, Jean E, Caldas, Carlos, Rassl, Doris M, Rintoul, Robert C, Alifrangis, Constantine, Middleton, Mark R, Gallagher, Ferdia A, Parkinson, Christine, Durrani, Amer, McDermott, Ultan, Smith, Christopher G, Massie, Charles, Corrie, Pippa G, Rosenfeld, Nitzan
Format:	Journal Article
Language:	English
Published:	United States 17.06.2020
Subjects:	Biomarkers, Tumor Circulating Tumor DNA - genetics DNA, Neoplasm - genetics High-Throughput Nucleotide Sequencing Humans Liquid Biopsy Mutation - genetics
ISSN:	1946-6242, 1946-6242
Online Access:	Get more information
Tags:	Add Tag No Tags, Be the first to tag this record!

Abstract	Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >10 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.
AbstractList	Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >105 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies. Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume or residual disease, where plasma contains very few tumor-derived DNA fragments. We show that sensitivity for ctDNA detection in plasma can be improved by analyzing hundreds to thousands of mutations that are first identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) pipeline, which combines custom error-suppression methods and signal-enrichment approaches based on biological features of ctDNA. With this approach, the detection limit in each sample can be estimated independently based on the number of informative reads sequenced across multiple patient-specific loci. We applied INVAR to custom hybrid-capture sequencing data from 176 plasma samples from 105 patients with melanoma, lung, renal, glioma, and breast cancer across both early and advanced disease. By integrating signal across a median of >10 informative reads, ctDNA was routinely quantified to 1 mutant molecule per 100,000, and in some cases with high tumor mutation burden and/or plasma input material, to parts per million. This resulted in median area under the curve (AUC) values of 0.98 in advanced cancers and 0.80 in early-stage and challenging settings for ctDNA detection. We generalized this method to whole-exome and whole-genome sequencing, showing that INVAR may be applied without requiring personalized sequencing panels so long as a tumor mutation list is available. As tumor sequencing becomes increasingly performed, such methods for personalized cancer monitoring may enhance the sensitivity of cancer liquid biopsies.
Author	Barker, Emily Heider, Katrin Corrie, Pippa G Rosenfeld, Nitzan Gale, Davina Mair, Richard Parkinson, Christine Young, Gemma Smith, Christopher G Murphy, Suzanne McDermott, Ultan Fisher, Eyal Chandrananda, Dineika Ruiz-Valdepenas, Andrea Caldas, Carlos Abraham, Jean E Gallagher, Ferdia A Rintoul, Robert C Morris, James Brindle, Kevin M Durrani, Amer Massie, Charles Mouliere, Florent Alifrangis, Constantine Marshall, Andrea Gill, Andrew B Rassl, Doris M Chan, Pui Ying Hudecova, Irena Stewart, Grant D Wan, Jonathan C M Santonja, Angela Cooper, Wendy N Marass, Francesco Middleton, Mark R
Author_xml	– sequence: 1 givenname: Jonathan C M orcidid: 0000-0003-0001-1802 surname: Wan fullname: Wan, Jonathan C M organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 2 givenname: Katrin orcidid: 0000-0003-4035-1668 surname: Heider fullname: Heider, Katrin organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 3 givenname: Davina orcidid: 0000-0002-4521-8199 surname: Gale fullname: Gale, Davina organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 4 givenname: Suzanne surname: Murphy fullname: Murphy, Suzanne organization: Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK – sequence: 5 givenname: Eyal orcidid: 0000-0003-3546-6153 surname: Fisher fullname: Fisher, Eyal organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 6 givenname: Florent orcidid: 0000-0001-7043-0514 surname: Mouliere fullname: Mouliere, Florent organization: Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands – sequence: 7 givenname: Andrea surname: Ruiz-Valdepenas fullname: Ruiz-Valdepenas, Andrea organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 8 givenname: Angela orcidid: 0000-0001-9367-7632 surname: Santonja fullname: Santonja, Angela organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 9 givenname: James surname: Morris fullname: Morris, James organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 10 givenname: Dineika orcidid: 0000-0002-8834-9500 surname: Chandrananda fullname: Chandrananda, Dineika organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 11 givenname: Andrea orcidid: 0000-0002-6610-5812 surname: Marshall fullname: Marshall, Andrea organization: Warwick Clinical Trials Unit, University of Warwick, Coventry CV4 7AL, UK – sequence: 12 givenname: Andrew B orcidid: 0000-0002-9287-9563 surname: Gill fullname: Gill, Andrew B organization: Department of Radiology, University of Cambridge, Cambridge CB2 0QQ, UK – sequence: 13 givenname: Pui Ying orcidid: 0000-0001-7804-4482 surname: Chan fullname: Chan, Pui Ying organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 14 givenname: Emily orcidid: 0000-0001-6682-0392 surname: Barker fullname: Barker, Emily organization: Cambridge Clinical Trials Unit-Cancer Theme, Cambridge CB2 0QQ, UK – sequence: 15 givenname: Gemma surname: Young fullname: Young, Gemma organization: Cambridge Clinical Trials Unit-Cancer Theme, Cambridge CB2 0QQ, UK – sequence: 16 givenname: Wendy N orcidid: 0000-0003-3416-9982 surname: Cooper fullname: Cooper, Wendy N organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 17 givenname: Irena orcidid: 0000-0003-3823-9896 surname: Hudecova fullname: Hudecova, Irena organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 18 givenname: Francesco orcidid: 0000-0002-8993-7320 surname: Marass fullname: Marass, Francesco organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 19 givenname: Richard orcidid: 0000-0001-8235-5689 surname: Mair fullname: Mair, Richard organization: Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK – sequence: 20 givenname: Kevin M orcidid: 0000-0003-3883-6287 surname: Brindle fullname: Brindle, Kevin M organization: Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK – sequence: 21 givenname: Grant D orcidid: 0000-0003-3188-9140 surname: Stewart fullname: Stewart, Grant D organization: Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK – sequence: 22 givenname: Jean E orcidid: 0000-0003-0688-4807 surname: Abraham fullname: Abraham, Jean E organization: Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK – sequence: 23 givenname: Carlos orcidid: 0000-0003-3547-1489 surname: Caldas fullname: Caldas, Carlos organization: Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK – sequence: 24 givenname: Doris M surname: Rassl fullname: Rassl, Doris M organization: Royal Papworth Hospital NHS Foundation Trust, Cambridge CB2 0AY, UK – sequence: 25 givenname: Robert C surname: Rintoul fullname: Rintoul, Robert C organization: Department of Oncology, University of Cambridge Hutchison-MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK – sequence: 26 givenname: Constantine orcidid: 0000-0002-5876-6696 surname: Alifrangis fullname: Alifrangis, Constantine organization: Wellcome Sanger Institute, Hinxton CB10 1SA, UK – sequence: 27 givenname: Mark R orcidid: 0000-0003-0167-1685 surname: Middleton fullname: Middleton, Mark R organization: National Institute for Health Research Biomedical Research Centre, Oxford OX4 2PG, UK – sequence: 28 givenname: Ferdia A orcidid: 0000-0003-4784-5230 surname: Gallagher fullname: Gallagher, Ferdia A organization: Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands – sequence: 29 givenname: Christine surname: Parkinson fullname: Parkinson, Christine organization: Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK – sequence: 30 givenname: Amer surname: Durrani fullname: Durrani, Amer organization: Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK – sequence: 31 givenname: Ultan orcidid: 0000-0001-9032-4700 surname: McDermott fullname: McDermott, Ultan organization: Wellcome Sanger Institute, Hinxton CB10 1SA, UK – sequence: 32 givenname: Christopher G orcidid: 0000-0001-7357-2737 surname: Smith fullname: Smith, Christopher G organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 33 givenname: Charles orcidid: 0000-0003-2314-4843 surname: Massie fullname: Massie, Charles organization: Department of Oncology, University of Cambridge Hutchison-MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK – sequence: 34 givenname: Pippa G orcidid: 0000-0003-4875-7021 surname: Corrie fullname: Corrie, Pippa G organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK – sequence: 35 givenname: Nitzan orcidid: 0000-0002-2825-4788 surname: Rosenfeld fullname: Rosenfeld, Nitzan email: nitzan.rosenfeld@cruk.cam.ac.uk organization: Cancer Research UK Major Centre-Cambridge, Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/32554709$$D View this record in MEDLINE/PubMed
BookMark	eNpNkEtLxDAUhYOMOA_9ByJduqkmaR7tchifMOhCXZckvR0ibVKTVNBfbwdHcHPPhftxOPcs0cx5BwidE3xFCBXX0dgUlItdD82VUt8lLtkRWpCKiVxQRmf_9jlaxviOsSgLLk7QvKCcM4mrBXox6eZpnfXe2eSDdbtsjPs5qGTBpTwOYGxrTRbhYwRn9jflmsy6BLswQd5lvs0-VbDKpSyAauIpOm5VF-HsoCv0dnf7unnIt8_3j5v1NjeMyZQTqHAxvaIJY5xwLRkIDLRstdQNx6LiYCQpgVRaccHEpMYUUhvcGKWxoSt0-es7BD-Fi6nubTTQdcqBH2NNGeG0kpLxCb04oKOe-qqHYHsVvuq_IugP_Yll6g
CitedBy_id	crossref_primary_10_1186_s13059_023_02920_1 crossref_primary_10_1038_s41598_022_05606_z crossref_primary_10_1186_s13059_023_03074_w crossref_primary_10_1177_17588359231192401 crossref_primary_10_1186_s13073_021_00902_1 crossref_primary_10_1038_s41523_024_00653_3 crossref_primary_10_3390_cancers16233919 crossref_primary_10_1016_j_acra_2024_03_019 crossref_primary_10_1080_13102818_2023_2287236 crossref_primary_10_1186_s12943_022_01551_7 crossref_primary_10_15252_emmm_202217282 crossref_primary_10_3390_ijms25073867 crossref_primary_10_15252_emmm_202216505 crossref_primary_10_3389_fgene_2021_811291 crossref_primary_10_3390_genes16080962 crossref_primary_10_3390_cancers17091442 crossref_primary_10_1016_j_jmoldx_2024_08_004 crossref_primary_10_1002_1878_0261_13267 crossref_primary_10_1016_j_ejca_2023_113455 crossref_primary_10_1158_1078_0432_CCR_22_3526 crossref_primary_10_1515_oncologie_2024_0594 crossref_primary_10_3390_cancers14184359 crossref_primary_10_15252_emmm_202012881 crossref_primary_10_3389_fonc_2021_662094 crossref_primary_10_1016_j_annonc_2022_02_007 crossref_primary_10_1016_j_ccell_2023_08_010 crossref_primary_10_1038_s41467_022_32598_1 crossref_primary_10_3390_ijms222011267 crossref_primary_10_1007_s11864_021_00882_9 crossref_primary_10_1158_2159_8290_CD_21_0634 crossref_primary_10_1136_jclinpath_2020_206745 crossref_primary_10_1016_j_yamp_2024_06_005 crossref_primary_10_1038_s41416_021_01507_6 crossref_primary_10_1200_EDBK_358995 crossref_primary_10_3390_diagnostics11010073 crossref_primary_10_1038_s41591_024_03040_4 crossref_primary_10_1093_nar_gkab1222 crossref_primary_10_1016_j_esmogo_2024_100068 crossref_primary_10_1038_s41551_022_00855_9 crossref_primary_10_1016_j_pan_2020_12_017 crossref_primary_10_3390_cancers12123493 crossref_primary_10_3390_cancers16132432 crossref_primary_10_1007_s11426_023_1727_9 crossref_primary_10_3390_ijms252413349 crossref_primary_10_3390_ijms25084252 crossref_primary_10_1002_ijc_34964 crossref_primary_10_1139_bcb_2024_0004 crossref_primary_10_3390_biomedicines10051181 crossref_primary_10_3390_cancers17060977 crossref_primary_10_3390_cancers14133275 crossref_primary_10_1002_1878_0261_13116 crossref_primary_10_1093_neuonc_noac127 crossref_primary_10_1016_j_isci_2024_110330 crossref_primary_10_1186_s13073_020_00770_1 crossref_primary_10_1038_s41587_021_00981_w crossref_primary_10_1080_14737159_2021_1889371 crossref_primary_10_1016_j_tips_2025_08_001 crossref_primary_10_1038_s41571_022_00664_8 crossref_primary_10_3390_cancers13184500 crossref_primary_10_1038_s41416_021_01635_z crossref_primary_10_3390_cancers14092052 crossref_primary_10_1016_j_euros_2021_12_006 crossref_primary_10_1016_j_jlb_2024_100141 crossref_primary_10_1136_jitc_2025_012034 crossref_primary_10_1093_clinchem_hvac095 crossref_primary_10_1016_j_neo_2021_06_005 crossref_primary_10_1158_0008_5472_CAN_23_2557 crossref_primary_10_25259_IJMR_1291_2024 crossref_primary_10_3390_cancers14020288 crossref_primary_10_1039_D1NR07845C crossref_primary_10_1038_s41525_024_00415_x crossref_primary_10_1016_j_crad_2021_07_005 crossref_primary_10_1002_1878_0261_70116 crossref_primary_10_1038_s41416_022_01769_8 crossref_primary_10_1126_science_adf2341 crossref_primary_10_1186_s12885_022_09387_6 crossref_primary_10_3390_cancers16091681 crossref_primary_10_1016_j_medj_2021_11_001 crossref_primary_10_1038_s41416_021_01646_w crossref_primary_10_1038_s41591_025_03577_y crossref_primary_10_1002_ijc_35152 crossref_primary_10_1038_s41416_021_01594_5 crossref_primary_10_1158_2159_8290_CD_20_1311 crossref_primary_10_1093_neuonc_noab012 crossref_primary_10_1080_14737159_2025_2498545 crossref_primary_10_1158_1078_0432_CCR_21_1242 crossref_primary_10_1093_clinchem_hvac121 crossref_primary_10_1038_s41416_022_01723_8 crossref_primary_10_1038_s41571_025_01033_x crossref_primary_10_1016_j_critrevonc_2022_103725 crossref_primary_10_1016_j_bios_2023_115611 crossref_primary_10_1038_s41416_021_01696_0 crossref_primary_10_1515_medgen_2023_2065 crossref_primary_10_1515_medgen_2023_2064 crossref_primary_10_2147_CMAR_S335679 crossref_primary_10_1186_s12859_023_05478_8 crossref_primary_10_1016_j_eururo_2024_01_002 crossref_primary_10_3389_fcell_2020_622579 crossref_primary_10_1007_s11912_021_01151_6 crossref_primary_10_3390_cancers16010082 crossref_primary_10_1016_j_tig_2023_01_004 crossref_primary_10_37349_etat_2025_1002333 crossref_primary_10_1016_j_oraloncology_2024_106717 crossref_primary_10_3389_fimmu_2024_1509968 crossref_primary_10_15252_emmm_202215729 crossref_primary_10_1016_j_ejca_2021_09_019 crossref_primary_10_1002_adma_202207282 crossref_primary_10_3390_ijms241311026 crossref_primary_10_1016_j_tranon_2023_101701 crossref_primary_10_3390_ijms221910373 crossref_primary_10_1038_s41467_024_52923_0 crossref_primary_10_3389_fonc_2022_900945 crossref_primary_10_1007_s40291_021_00534_6 crossref_primary_10_1016_j_oraloncology_2024_107111 crossref_primary_10_7554_eLife_64356 crossref_primary_10_1002_1878_0261_12983 crossref_primary_10_1186_s13059_025_03607_5 crossref_primary_10_1186_s12967_025_06993_3
ContentType	Journal Article
Copyright	Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Copyright_xml	– notice: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
DBID	CGR CUY CVF ECM EIF NPM 7X8
DOI	10.1126/scitranslmed.aaz8084
DatabaseName	Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic
DatabaseTitle	MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	no_fulltext_linktorsrc
Discipline	Medicine
EISSN	1946-6242
ExternalDocumentID	32554709
Genre	Research Support, Non-U.S. Gov't Journal Article
GrantInformation_xml	– fundername: Cancer Research UK grantid: 27150 – fundername: Cancer Research UK grantid: 26886 – fundername: Cancer Research UK grantid: 26718 – fundername: Cancer Research UK grantid: C2195/A8466 – fundername: Cancer Research UK grantid: C7535/A6408 – fundername: Cancer Research UK grantid: 20240 – fundername: Cancer Research UK grantid: 28292 – fundername: Cancer Research UK grantid: 17242 – fundername: Cancer Research UK grantid: 16628 – fundername: Cancer Research UK grantid: 27548
GroupedDBID	--- 0R~ 4.4 53G 7~K ABJNI ACGFS AENEX AFQFN AJGZS AJWWR ALMA_UNASSIGNED_HOLDINGS BKF C45 CGR CUY CVF DU5 EBS ECM EIF EMOBN F5P HZ~ NPM O9- OFXIZ OVD OVIDX P2P RHI TEORI 7X8
ID	FETCH-LOGICAL-c447t-1e903112b144515b74e60e28fb7bd50695ec718e19ba564619bcc37bc0dcab0c2
IEDL.DBID	7X8
ISICitedReferencesCount	139
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000542222000004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	1946-6242
IngestDate	Fri Sep 05 07:11:50 EDT 2025 Sat May 31 02:12:46 EDT 2025
IsDoiOpenAccess	false
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Issue	548
Language	English
License	Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c447t-1e903112b144515b74e60e28fb7bd50695ec718e19ba564619bcc37bc0dcab0c2
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ORCID	0000-0001-6682-0392 0000-0002-2825-4788 0000-0002-6610-5812 0000-0001-7804-4482 0000-0003-3823-9896 0000-0002-9287-9563 0000-0003-3883-6287 0000-0002-8993-7320 0000-0003-0001-1802 0000-0003-3416-9982 0000-0003-3546-6153 0000-0003-2314-4843 0000-0001-7043-0514 0000-0001-8235-5689 0000-0003-0688-4807 0000-0001-9032-4700 0000-0003-4784-5230 0000-0001-9367-7632 0000-0003-0167-1685 0000-0002-4521-8199 0000-0003-3547-1489 0000-0001-7357-2737 0000-0003-4875-7021 0000-0003-4035-1668 0000-0002-5876-6696 0000-0002-8834-9500 0000-0003-3188-9140
OpenAccessLink	http://hdl.handle.net/11343/254094
PMID	32554709
PQID	2415297745
PQPubID	23479
ParticipantIDs	proquest_miscellaneous_2415297745 pubmed_primary_32554709
PublicationCentury	2000
PublicationDate	2020-06-17 20200617
PublicationDateYYYYMMDD	2020-06-17
PublicationDate_xml	– month: 06 year: 2020 text: 2020-06-17 day: 17
PublicationDecade	2020
PublicationPlace	United States
PublicationPlace_xml	– name: United States
PublicationTitle	Science translational medicine
PublicationTitleAlternate	Sci Transl Med
PublicationYear	2020
SSID	ssj0068356
Score	2.6261978
Snippet	Circulating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Detection of ctDNA can be challenging in patients with low-volume...
SourceID	proquest pubmed
SourceType	Aggregation Database Index Database
SubjectTerms	Biomarkers, Tumor Circulating Tumor DNA - genetics DNA, Neoplasm - genetics High-Throughput Nucleotide Sequencing Humans Liquid Biopsy Mutation - genetics
Title	ctDNA monitoring using patient-specific sequencing and integration of variant reads
URI	https://www.ncbi.nlm.nih.gov/pubmed/32554709 https://www.proquest.com/docview/2415297745
Volume	12
WOSCitedRecordID	wos000542222000004&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText
inHoldings	1
isFullTextHit
isPrint
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1JS8QwFA7qiHhxX8aNCF6j3ZOcZFAHD04ZUGFuQ5KmImg72joHf73vZTJ6EgQvvZSS8pa8_XuEnIm0VIlWAZPcaAxQLNNFGjCTIHxdrCJpHWT-Hc9zMRrJoU-4Nb6tcn4nuou6qA3myC-cpUFnJb2cvDHcGoXVVb9CY5F0YnBlsKWLj76rCBl4F266SCYZwzkIPzrnh2ZaNAYvYHPOlfoUDt_0NyfTGZv--n9_c4OseTeT9mZysUkWbLVFVga-kL5N7k17nffoq9NoTO1RbIB_oh5mleEAJjYRUd9qje9UVdA5ugRwk9YlnUKkDayh4HkWzQ557N88XN0yv18BOJHwloVWgkqHkQ4RpSzVPLFZYCNRao78ymRqDZguG0qt0iyBUEsbE3NtgsIoHZholyxVdWX3CUUgKiEKLTA-EWEgIwVHxCW3UhWCl11yOifXGOQXixKqsvVHM_4hWJfszWg-nsyANsYxxDsJD-TBH74-JKsRhsK4VogfkU4J2muPybKZts_N-4kTDHjmw8EXVMvEcA
linkProvider	ProQuest
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=ctDNA+monitoring+using+patient-specific+sequencing+and+integration+of+variant+reads&rft.jtitle=Science+translational+medicine&rft.au=Wan%2C+Jonathan+C+M&rft.au=Heider%2C+Katrin&rft.au=Gale%2C+Davina&rft.au=Murphy%2C+Suzanne&rft.date=2020-06-17&rft.issn=1946-6242&rft.eissn=1946-6242&rft.volume=12&rft.issue=548&rft_id=info:doi/10.1126%2Fscitranslmed.aaz8084&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1946-6242&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1946-6242&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1946-6242&client=summon