Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17:223–38.

CAS  PubMed  Google Scholar 

Cescon DW, Bratman SV, Chan SM, Siu LL. Circulating tumor DNA and liquid biopsy in oncology. Nat Cancer. 2020;1:276–90.

CAS  PubMed  Google Scholar 

Babayan A, Pantel K. Advances in liquid biopsy approaches for early detection and monitoring of cancer. Genome Med. 2018;10:4–6.

Google Scholar 

Bedard PL, Hansen AR, Ratain MJ, Siu LL. Tumour heterogeneity in the clinic. Nature. 2013;501:355–64.

CAS  PubMed  PubMed Central  Google Scholar 

Abbosh C, Birkbak NJ, Wilson GA, Jamal-Hanjani M, Constantin T, Salari R, et al. Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017;545:446–51.

CAS  PubMed  PubMed Central  Google Scholar 

Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019;20:71–88.

CAS  PubMed  Google Scholar 

Alix-Panabières C, Pantel K. Liquid biopsy: from discovery to clinical application. Cancer Discov. 2021;11:858–73.

PubMed  Google Scholar 

Im YR, Tsui DWY, Diaz LA, Wan JCM. Next-generation liquid biopsies: embracing data science in oncology. Trends Cancer. 2021;7:283–92.

CAS  PubMed  Google Scholar 

Diaz LA, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol. 2014;32:579–86.

Thierry AR, El Messaoudi S, Gahan PB, Anker P, Stroun M. Origins, structures, and functions of circulating DNA in oncology. Cancer Metastasis Rev. 2016;35:347–76.

Han X, Wang J, Sun Y. Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics. 2017;15:59–72.

Fu Y, Yang Z, Hu Z, Yang Z, Pan Y, Chen J, et al. Preoperative serum ctDNA predicts early hepatocellular carcinoma recurrence and response to systemic therapies. Hepatol Int. 2022;16:868–78.

Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:904–16.

CAS  PubMed  PubMed Central  Google Scholar 

Jia J, Morse MA, Nagy RJ, Lanman RB, Strickler JH. Cell-free DNA profiling to discover mechanisms of exceptional response to cabozantinib plus panitumumab in a patient with treatment refractory metastatic colorectal cancer. Front Oncol. 2018;8:305.

Georgiadis A, Durham JN, Keefer LA, Bartlett BR, Zielonka M, Murphy D, et al. Noninvasive detection of microsatellite instability and high tumor mutation burden in cancer patients treated with PD-1 blockade. Clin Cancer Res. 2019;25:7024–34.

PubMed  PubMed Central  Google Scholar 

Lennon AM, Buchanan AH, Kinde I, Warren A, Honushefsky A, Cohain AT, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020;369:eabb9601.

Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV, Liu MC, et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020;31:745–59.

CAS  PubMed  Google Scholar 

Chen L, Abou-Alfa GK, Zheng B, Liu JF, Bai J, Du LT, et al. Genome-scale profiling of circulating cell-free DNA signatures for early detection of hepatocellular carcinoma in cirrhotic patients. Cell Res. 2021;31:589–92.

CAS  PubMed  PubMed Central  Google Scholar 

Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H, Azad TD, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 2017;7:1394–403.

CAS  PubMed  PubMed Central  Google Scholar 

Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5:1124–31.

PubMed  PubMed Central  Google Scholar 

Chen G, Peng J, Xiao Q, Wu HX, Wu X, Wang F, et al. Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. J Hematol Oncol. 2021;14:80.

Kilgour E, Rothwell DG, Brady G, Dive C. Liquid biopsy-based biomarkers of treatment response and resistance. Cancer Cell. 2020;37:485–95.

CAS  PubMed  Google Scholar 

De Rubis G, Rajeev Krishnan S, Bebawy M. Liquid biopsies in cancer diagnosis, monitoring, and prognosis. Trends Pharmacol Sci. 2019;40:172–86.

PubMed  Google Scholar 

Ignatiadis M, Sledge GW, Jeffrey, SS. Liquid biopsy enters the clinic—implementation issues and future challenges. Nat Rev Clin Oncol. 2021;18:297–31.

Snyder MW, Kircher M, Hill AJ, Daza RM, Correspondence JS. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell. 2016;164:57–68.

CAS  PubMed  PubMed Central  Google Scholar 

Costello JF, Frühwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet. 2000;24:132–8.

CAS  PubMed  Google Scholar 

Shen SY, Singhania R, Fehringer G, Chakravarthy A, Roehrl MHA, Chadwick D, et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature. 2018;563:579–83.

CAS  PubMed  Google Scholar 

Garrigou S, Perkins G, Garlan F, Normand C, Didelot A, Le Corre D, et al. A study of hypermethylated circulating tumor DNA as a universal colorectal cancer biomarker. Clin Chem. 2016;62:1129–39.

CAS  PubMed  Google Scholar 

Pietrasz D, Wang-Renault S, Taieb J, Dahan L, Postel M, Durand-Labrunie J, et al. Prognostic value of circulating tumour DNA in metastatic pancreatic cancer patients: post-hoc analyses of two clinical trials. Br J Cancer. 2021;126:440–8.

PubMed  Google Scholar 

Beinse G, Borghese B, Métairie M, Just P-A, Poulet G, Garinet S, et al. Highly specific droplet-digital PCR detection of universally methylated circulating tumor DNA in endometrial carcinoma. Clin Chem. 2022. https://doi.org/10.1093/CLINCHEM/HVAC020.

Tan HT, Low J, Lim SG, Chung MCM. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276:6880–904.

CAS  PubMed  Google Scholar 

Cristiano S, Leal A, Phallen J, Fiksel J, Adleff V, Bruhm DC, et al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature. 2019;570:385–9.

CAS  PubMed  PubMed Central  Google Scholar 

Heider K, Wan JCM, Hall J, Belic J, Boyle S, Hudecova I, et al. Detection of ctDNA from dried blood spots after DNA size selection. Clin Chem. 2020;66:697–705.

PubMed  Google Scholar 

Mouliere F, Chandrananda D, Piskorz AM, Moore EK, Morris J, Barlebo Ahlborn L, et al. Enhanced detection of circulating tumor DNA by fragment size analysis. Sci Transl Med. 2018;10:4921.

Google Scholar 

Jiang P, Sun K, Peng W, Cheng SH, Ni M, Yeung PC, et al. Plasma DNA end-motif profiling as a fragmentomic marker in cancer, pregnancy, and transplantation. Cancer Discov. 2020;10:664–73.

CAS  PubMed  Google Scholar 

Larson MH, Pan W, Kim HJ, Mauntz RE, Stuart SM, Pimentel M, et al. A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection. Nat Commun. 2021;12:2357.

Poore GD, Kopylova E, Zhu Q, Carpenter C, Fraraccio S, Wandro S, et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature. 2020;579:567–74.

CAS  PubMed  PubMed Central  Google Scholar 

Mathios D, Johansen JS, Cristiano S, Medina JE, Phallen J, Larsen KR, et al. Detection and characterization of lung cancer using cell-free DNA fragmentomes. Nat Commun. 2021;12:5060.

CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Ma L, Wu D, Chen G. Advances in bulk and single-cell multi-omics approaches for systems biology and precision medicine. Brief Bioinform. 2021;22:1–18.

Google Scholar 

Amelio I, Bertolo R, Bove P, Buonomo OC, Candi E, Chiocchi M, et al. Liquid biopsies and cancer omics. Cell Death Discov. 2020;6:131.

Greenberg MVC, Bourc’his D. The diverse roles of DNA methylation in mammalian development and disease. Nat Rev Mol Cell Biol. 2019;20:590–607.

CAS  PubMed  Google Scholar 

Zaporozhchenko IA, Ponomaryova AA, Rykova EY, Laktionov PP. The potential of circulating cell-free RNA as a cancer biomarker: challenges and opportunities. Expert Rev Mol Diagn. 2018;18:133–45.

CAS  PubMed  Google Scholar 

Geary B, Walker MJ, Snow JT, Lee DCH, Pernemalm M, Maleki-Dizaji S, et al. Identification of a biomarker panel for early detection of lung cancer patients. J Proteome Res. 2019;18:3369–82.

CAS  PubMed  Google Scholar 

Peng L, Cantor DI, Huang C, Wang K, Baker MS, Nice EC. Tissue and plasma proteomics for early stage cancer detection. Mol Omics. 2018;14:405–23.

CAS  PubMed  Google Scholar 

Chen F, Dai X, Zhou C-C, Li K, Zhang Y, Lou X-Y, et al. Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma. Gut. 2021. https://doi.org/10.1136/gutjnl-2020-323476.

Dawson S-J, Tsui DWY, Murtaza M, Biggs H, Rueda OM, Chin S-F, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368:1199–209.

CAS  PubMed  Google Scholar 

Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S, Cutts RJ, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7:1–12.

Google Scholar 

Diehl F, Li M, Dressman D, He Y, Shen D, Szabo S, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci USA. 2005;102:16368–73.

CAS  PubMed  PubMed Central  Google Scholar 

Newman AM, Bratman SV, To J, Wynne JF, Eclov NCW, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20:548–54.

CAS  PubMed  PubMed Central  Google Scholar 

Phallen J, Sausen M, Adleff V, Leal A, Hruban C, White J, et al. Direct detection of early-stage cancers using circulating tumor DNA. Sci Transl Med. 2017;9:eaan2415.

Razavi P, Li BT, Brown DN, Jung B, Hubbell E, Shen R, et al. High-intensity sequencing reveals the sources of plasma circulating cell-free DNA variants. Nat Med. 2019;25:1928–37.

CAS  PubMed  PubMed Central  Google Scholar 

Lianidou E. Detection and relevance of epigenetic markers on ctDNA: recent advances and future outlook. Mol Oncol. 2021;15:1683–1700.

CAS  PubMed  PubMed Central  Google Scholar 

Dor Y, Cedar H. Principles of DNA methylation and their implications for biology and medicine. Lancet. 2018;392:777–86.

CAS  PubMed  Google Scholar 

Venegas V, Halberg MC. Quantification of mtDNA mutation heteroplasmy (ARMS qPCR). Methods Mol Biol. 2012;837:313–26.