1932

Abstract

Roughly 70 years after the presence of cell-free DNA (cfDNA) in circulating blood was discovered, cfDNA has emerged as a transformative technology in clinical oncology. The ability to assess the presence, level, and composition of tumor DNA from a routine, noninvasive blood draw has opened the door to a broad array of high-impact clinical applications. While cfDNA is rapidly gaining clinical favor as a means of tumor mutational profiling without the need for an invasive biopsy, emerging applications in the areas of clinical monitoring and early cancer detection hold tremendous promise. These developing applications of cfDNA are reviewed herein.

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2019-03-04
2024-04-15
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Literature Cited

  1. Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG et al. 2017. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nat. Commun. 8:1324
    [Google Scholar]
  2. Andre T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F et al. 2015. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J. Clin. Oncol. 33:4176–87
    [Google Scholar]
  3. Bailey MH, Tokheim C, Porta-Pardo E, Sengupta S, Bertrand D et al. 2018. Comprehensive characterization of cancer driver genes and mutations. Cell 173:371–85.e18
    [Google Scholar]
  4. Benson AB 3rd, Venook AP, Cederquist L, Chan E, Chen YJ et al. 2017. Colon cancer, version 1.2017: NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 15:370–98
    [Google Scholar]
  5. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y et al. 2014. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6:224ra24
    [Google Scholar]
  6. Bhang HE, Ruddy DA, Krishnamurthy Radhakrishna V, Caushi JX, Zhao R et al. 2015. Studying clonal dynamics in response to cancer therapy using high-complexity barcoding. Nat. Med. 21:440–48
    [Google Scholar]
  7. Cancer Genome Atlas Res. Netw. 2014. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–9
    [Google Scholar]
  8. Catalona WJ, Smith DS, Ornstein DK 1997. Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination: enhancement of specificity with free PSA measurements. JAMA 277:1452–55
    [Google Scholar]
  9. Chabon JJ, Simmons AD, Lovejoy AF, Esfahani MS, Newman AM et al. 2016. Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat. Commun. 7:11815
    [Google Scholar]
  10. Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ et al. 2017. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N. Engl. J. Med. 377:513–22
    [Google Scholar]
  11. Chandarlapaty S, Chen D, He W, Sung P, Samoila A et al. 2016. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer: a secondary analysis of the BOLERO-2 clinical trial. JAMA Oncol 2:1310–15
    [Google Scholar]
  12. Chaudhuri AA, Chabon JJ, Lovejoy AF, Newman AM, Stehr H et al. 2017. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov 7:1394–403
    [Google Scholar]
  13. Cohen JD, Li L, Wang Y, Thoburn C, Afsari B et al. 2018. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science 359:926–30
    [Google Scholar]
  14. Corcoran RB, Andre T, Atreya CE, Schellens JHM, Yoshino T et al. 2018. Combined BRAF, EGFR, and MEK inhibition in patients with BRAFV600E-mutant colorectal cancer. Cancer Discov 8:428–43
    [Google Scholar]
  15. Corcoran RB, Dias-Santagata D, Bergethon K, Iafrate AJ, Settleman J, Engelman JA 2010. BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation. Sci. Signal 3:ra84
    [Google Scholar]
  16. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM et al. 2013. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med. 368:1199–209
    [Google Scholar]
  17. Diaz LA Jr., Williams RT, Wu J, Kinde I, Hecht JR et al. 2012. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 486:537–40
    [Google Scholar]
  18. Diehl F, Li M, He Y, Kinzler KW, Vogelstein B, Dressman D 2006. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat. Methods 3:551–59
    [Google Scholar]
  19. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S et al. 2008. Circulating mutant DNA to assess tumor dynamics. Nat. Med. 14:985–90
    [Google Scholar]
  20. Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J et al. 2017. Non–small cell lung cancer, version 5.2017: NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Cancer Netw. 15:504–35
    [Google Scholar]
  21. Fan HC, Blumenfeld YJ, Chitkara U, Hudgins L, Quake SR 2010. Analysis of the size distributions of fetal and maternal cell-free DNA by paired-end sequencing. Clin. Chem. 56:1279–86
    [Google Scholar]
  22. Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DW et al. 2012. Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci. Transl. Med. 4:136ra68
    [Google Scholar]
  23. Garcia-Murillas I, Schiavon G, Weigelt B, Ng C, Hrebien S et al. 2015. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci. Transl. Med. 7:302ra133
    [Google Scholar]
  24. Garraway LA, Janne PA 2012. Circumventing cancer drug resistance in the era of personalized medicine. Cancer Discov 2:214–26
    [Google Scholar]
  25. Genovese G, Kahler AK, Handsaker RE, Lindberg J, Rose SA et al. 2014. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N. Engl. J. Med. 371:2477–87
    [Google Scholar]
  26. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D et al. 2012. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366:883–92
    [Google Scholar]
  27. Goyal L, Saha SK, Liu LY, Siravegna G, Leshchiner I et al. 2017. Polyclonal secondary FGFR2 mutations drive acquired resistance to FGFR inhibition in patients with FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov 7:252–63
    [Google Scholar]
  28. Hazar-Rethinam M, Kleyman M, Han GC, Liu D, Ahronian LG et al. 2018. Convergent therapeutic strategies to overcome the heterogeneity of acquired resistance in BRAFV600E colorectal cancer. Cancer Discov 8:417–27
    [Google Scholar]
  29. Hindson BJ, Ness KD, Masquelier DA, Belgrader P, Heredia NJ et al. 2011. High-throughput droplet digital PCR system for absolute quantitation of DNA copy number. Anal. Chem. 83:8604–10
    [Google Scholar]
  30. Hu Y, Ulrich B, Supplee J, Kuang Y, Lizotte PH et al. 2018. False positive plasma genotyping due to clonal hematopoiesis. Clin. Cancer Res. 24:4437–43
    [Google Scholar]
  31. Husain H, Melnikova VO, Kosco K, Woodward B, More S et al. 2017. Monitoring daily dynamics of early tumor response to targeted therapy by detecting circulating tumor DNA in urine. Clin. Cancer Res. 23:4716–23
    [Google Scholar]
  32. Jaiswal S, Fontanillas P, Flannick J, Manning A, Grauman PV et al. 2014. Age-related clonal hematopoiesis associated with adverse outcomes. N. Engl. J. Med. 371:2488–98
    [Google Scholar]
  33. Juric D, Castel P, Griffith M, Griffith OL, Won HH et al. 2015. Convergent loss of PTEN leads to clinical resistance to a PI(3)Kα inhibitor. Nature 518:240–44
    [Google Scholar]
  34. Kinde I, Wu J, Papadopoulos N, Kinzler KW, Vogelstein B 2011. Detection and quantification of rare mutations with massively parallel sequencing. PNAS 108:9530–35
    [Google Scholar]
  35. Kuang Y, O'Connell A, Sacher AG, Feeney N, Alden RS et al. 2018. Monitoring of response and resistance in plasma of EGFR-mutant lung cancer using droplet digital PCR. Methods Mol. Biol. 1768:193–193
    [Google Scholar]
  36. Kwak EL, Ahronian LG, Siravegna G, Mussolin B, Godfrey JT et al. 2015. Molecular heterogeneity and receptor co-amplification drive resistance to targeted therapy in MET-amplified esophagogastric cancer. Cancer Discov 5:1271–81
    [Google Scholar]
  37. Lanman RB, Mortimer SA, Zill OA, Sebisanovic D, Lopez R et al. 2015. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLOS ONE 10:e0140712
    [Google Scholar]
  38. Leary RJ, Kinde I, Diehl F, Schmidt K, Clouser C et al. 2010. Development of personalized tumor biomarkers using massively parallel sequencing. Sci. Transl. Med. 2:20ra14
    [Google Scholar]
  39. Leary RJ, Sausen M, Kinde I, Papadopoulos N, Carpten JD et al. 2012. Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci. Transl. Med. 4:162ra54
    [Google Scholar]
  40. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ 1977. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–50
    [Google Scholar]
  41. Leygo C, Williams M, Jin HC, Chan MWY, Chu WK et al. 2017. DNA methylation as a noninvasive epigenetic biomarker for the detection of cancer. Dis. Markers 2017:3726595
    [Google Scholar]
  42. Liu L, Toung JM, Jassowicz AF, Vijayaraghavan R, Kang H et al. 2018. Targeted methylation sequencing of plasma cell-free DNA for cancer detection and classification. Ann. Oncol. 29:1445–53
    [Google Scholar]
  43. Malapelle U, Sirera R, Jantus-Lewintre E, Reclusa P, Calabuig-Farinas S et al. 2017. Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer. Expert Rev. Mol. Diagn. 17:209–15
    [Google Scholar]
  44. Mandel P, Metais P 1948. Les acides nucléiques du plasma sanguin chez l'homme. C.R. Seances Soc. Biol. Fil. 142:241–43
    [Google Scholar]
  45. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M et al. 2012. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 486:532–36
    [Google Scholar]
  46. Moran S, Martinez-Cardus A, Sayols S, Musulen E, Balana C et al. 2016. Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis. Lancet Oncol 17:1386–95
    [Google Scholar]
  47. Murtaza M, Dawson SJ, Pogrebniak K, Rueda OM, Provenzano E et al. 2015. Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer. Nat. Commun. 6:8760
    [Google Scholar]
  48. Murtaza M, Dawson SJ, Tsui DW, Gale D, Forshew T et al. 2013. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497:108–12
    [Google Scholar]
  49. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC et al. 2014. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat. Med. 20:548–54
    [Google Scholar]
  50. Newman AM, Lovejoy AF, Klass DM, Kurtz DM, Chabon JJ et al. 2016. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat. Biotechnol. 34:547–55
    [Google Scholar]
  51. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR et al. 2017. Cancer incidence and survival trends by subtype using data from the surveillance epidemiology and end results program, 1992–2013. Cancer Epidemiol. Biomarkers Prev. 26:632–41
    [Google Scholar]
  52. O'Leary B, Hrebien S, Morden JP, Beaney M, Fribbens C et al. 2018. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer. Nat. Commun. 9:896
    [Google Scholar]
  53. Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP et al. 2016. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. J. Clin. Oncol. 34:3375–82
    [Google Scholar]
  54. Parikh A, Goyal L, Hazar-Rethinam M, Siravegna G, Blaszkowsky L et al. 2017. Systematic liquid biopsy identifies novel and heterogeneous mechanisms of acquired resistance in gastrointestinal (GI) cancer patients. Ann. Oncol. 28:mdx262
    [Google Scholar]
  55. Piotrowska Z, Niederst MJ, Karlovich CA, Wakelee HA, Neal JW et al. 2015. Heterogeneity underlies the emergence of EGFRT790 wild-type clones following treatment of T790M-positive cancers with a third-generation EGFR inhibitor. Cancer Discov 5:713–22
    [Google Scholar]
  56. Russo M, Siravegna G, Blaszkowsky LS, Corti G, Crisafulli G et al. 2016. Tumor heterogeneity and lesion-specific response to targeted therapy in colorectal cancer. Cancer Discov 6:147–53
    [Google Scholar]
  57. Sausen M, Phallen J, Adleff V, Jones S, Leary RJ et al. 2015. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat. Commun. 6:7686
    [Google Scholar]
  58. Schiavon G, Hrebien S, Garcia-Murillas I, Cutts RJ, Pearson A et al. 2015. Analysis of ESR1 mutation in circulating tumor DNA demonstrates evolution during therapy for metastatic breast cancer. Sci. Transl. Med. 7:313ra182
    [Google Scholar]
  59. Schreuer M, Meersseman G, Van Den Herrewegen S, Jansen Y, Chevolet I et al. 2016. Quantitative assessment of BRAF V600 mutant circulating cell-free tumor DNA as a tool for therapeutic monitoring in metastatic melanoma patients treated with BRAF/MEK inhibitors. J. Transl. Med. 14:95
    [Google Scholar]
  60. Schrock AB, Pavlick DC, Klempner SJ, Chung JH, Forcier B et al. 2018. Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced cancers of the gastrointestinal tract or anus. Clin. Cancer Res. 24:1881–90
    [Google Scholar]
  61. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E et al. 2015. The genetic evolution of melanoma from precursor lesions. N. Engl. J. Med. 373:1926–36
    [Google Scholar]
  62. Shinkins B, Nicholson BD, Primrose J, Perera R, James T et al. 2017. The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: results from the FACS trial. PLOS ONE 12:e0171810
    [Google Scholar]
  63. Siegel RL, Miller KD, Jemal A 2018. Cancer statistics, 2018. CA Cancer J. Clin. 68:7–30
    [Google Scholar]
  64. Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A et al. 2015. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat. Med. 21:795–801
    [Google Scholar]
  65. Strickler JH, Loree JM, Ahronian LG, Parikh AR, Niedzwiecki D et al. 2018. Genomic landscape of cell-free DNA in patients with colorectal cancer. Cancer Discov 8:164–73
    [Google Scholar]
  66. Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D et al. 2015. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat. Med. 21:560–62
    [Google Scholar]
  67. Tie J, Wang Y, Tomasetti C, Li L, Springer S et al. 2016. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci. Transl. Med. 8:346ra92
    [Google Scholar]
  68. Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D et al. 2010. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 17:77–88
    [Google Scholar]
  69. Zhang BM, Aleshin A, Lin CY, Ford J, Zehnder JL, Suarez CJ 2017. IDH2 mutation in a patient with metastatic colon cancer. N. Engl. J. Med. 376:1991–92
    [Google Scholar]
  70. Zill OA, Greene C, Sebisanovic D, Siew LM, Leng J et al. 2015. Cell-free DNA next-generation sequencing in pancreatobiliary carcinomas. Cancer Discov 5:1040–48
    [Google Scholar]
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