{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:00:33Z","timestamp":1790510433340,"version":"4.1.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"33","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Berliner Krebsgesellschaft"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2021,8,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Genetic investigation of tumor heterogeneity and clonal evolution in solid cancers could be assisted by the analysis of liquid biopsies. However, tumors of various entities might release different quantities of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) into the bloodstream, potentially limiting the diagnostic potential of liquid biopsy in distinct tumor histologies. Patients with advanced colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), and melanoma (MEL) were enrolled in the study, representing tumors with different metastatic patterns. Mutation profiles of cfDNA, CTCs, and tumor tissue were assessed by panel sequencing, targeting 327 cancer-related genes. In total, 30 tissue, 18 cfDNA, and 7 CTC samples from 18 patients were sequenced. Best concordance between the mutation profile of tissue and cfDNA was achieved in CRC and MEL, possibly due to the remarkable heterogeneity of HNSCC (63%, 55% and 11%, respectively). Concordance especially depended on the amount of cfDNA used for library preparation. While 21 of 27 (78%) tissue mutations were retrieved in high-input cfDNA samples (30\u2013100\u2009ng, <jats:italic>N<\/jats:italic>\u2009=\u20098), only 4 of 65 (6%) could be detected in low-input samples (&lt;30\u2009ng, <jats:italic>N<\/jats:italic>\u2009=\u200910). CTCs were detected in 13 of 18 patients (72%). However, downstream analysis was limited by poor DNA quality, allowing targeted sequencing of only seven CTC samples isolated from four patients. Only one CTC sample reflected the mutation profile of the respective tumor. Private mutations, which were detected in CTCs but not in tissue, suggested the presence of rare subclones. Our pilot study demonstrated superiority of cfDNA- compared to CTC-based mutation profiling. It was further shown that CTCs may serve as additional means to detect rare subclones possibly involved in treatment resistance. Both findings require validation in a larger patient cohort.<\/jats:p>","DOI":"10.1038\/s41388-021-01928-w","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T15:04:35Z","timestamp":1625583875000},"page":"5204-5212","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Applicability of liquid biopsies to represent the mutational profile of tumor tissue from different cancer entities"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-0340","authenticated-orcid":false,"given":"Sandra","family":"Liebs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Eder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Klauschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Sch\u00fctte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-9979","authenticated-orcid":false,"given":"Marie-Laure","family":"Yaspo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Keilholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Tinhofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8590-9699","authenticated-orcid":false,"given":"Evelyn","family":"Kidess-Sigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Braunholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,6]]},"reference":[{"key":"1928_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/gm474","volume":"5","author":"E Kidess","year":"2013","unstructured":"Kidess E, Jeffrey SS. Circulating tumor cells versus tumor-derived cell-free DNA: rivals or partners in cancer care in the era of single-cell analysis? Genome Med. 2013;5:70.","journal-title":"Genome Med"},{"key":"1928_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0600-4","volume":"16","author":"PR Prasetyanti","year":"2017","unstructured":"Prasetyanti PR, Medema JP. Intra-tumor heterogeneity from a cancer stem cell perspective. Mol Cancer. 2017;16:41.","journal-title":"Mol Cancer"},{"key":"1928_CR3","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1056\/NEJMoa1113205","volume":"366","author":"M Gerlinger","year":"2012","unstructured":"Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012;366:883\u201392.","journal-title":"N Engl J Med"},{"key":"1928_CR4","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/bjc.2012.581","volume":"108","author":"R Fisher","year":"2013","unstructured":"Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013;108:479\u201385.","journal-title":"Br J Cancer"},{"key":"1928_CR5","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/nature11156","volume":"486","author":"S Misale","year":"2012","unstructured":"Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486:532\u20136.","journal-title":"Nature."},{"key":"1928_CR6","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3658","volume":"16","author":"LG Martelotto","year":"2014","unstructured":"Martelotto LG, Ng CKY, Piscuoglio S, Weigelt B, Reis-Filho JS. Breast cancer intra-tumor heterogeneity. Breast Cancer Res. 2014;16:210.","journal-title":"Breast Cancer Res"},{"key":"1928_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00728-3","volume":"12","author":"F Castro-Giner","year":"2020","unstructured":"Castro-Giner F, Aceto N. Tracking cancer progression: from circulating tumor cells to metastasis. Genome Med. 2020;12:31.","journal-title":"Genome Med"},{"key":"1928_CR8","doi-asserted-by":"crossref","unstructured":"Tayoun T, Faugeroux V, Oulhen M, Aberlenc A, Pawlikowska P, Farace F. CTC-derived models: a window into the seeding capacity of circulating tumor cells (CTCs). Cells. 2019;8:1145.","DOI":"10.3390\/cells8101145"},{"key":"1928_CR9","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/S0002-9440(10)65628-3","volume":"153","author":"KJ Luzzi","year":"1998","unstructured":"Luzzi KJ, MacDonald IC, Schmidt EE, Kerkvliet N, Morris VL, Chambers AF, et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol. 1998;153:865\u201373.","journal-title":"Am J Pathol"},{"key":"1928_CR10","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1200\/JCO.2012.45.2011","volume":"32","author":"LA Diaz Jr","year":"2014","unstructured":"Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA. J Clin Onco. 2014;32:579\u201386.","journal-title":"J Clin Onco"},{"key":"1928_CR11","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/nm.3870","volume":"21","author":"G Siravegna","year":"2015","unstructured":"Siravegna G, Mussolin B, Buscarino M, Corti G, Cassingena A, Crisafulli G, et al. Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients. Nat Med. 2015;21:795\u2013801.","journal-title":"Nat Med"},{"key":"1928_CR12","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1158\/2159-8290.CD-17-0891","volume":"8","author":"KH Khan","year":"2018","unstructured":"Khan KH, Cunningham D, Werner B, Vlachogiannis G, Spiteri I, Heide T, et al. Longitudinal liquid biopsy and mathematical modeling of clonal evolution forecast time to treatment failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial. Cancer Discov. 2018;8:1270\u201385.","journal-title":"Cancer Discov"},{"key":"1928_CR13","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1373\/clinchem.2014.224808","volume":"60","author":"JD Kuhlmann","year":"2020","unstructured":"Kuhlmann JD, Wimberger P, Bankfalvi A, Keller T, Sch\u00f6ler S, Aktas B, et al. ERCC1-positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum resistance. Clin Chem. 2020;60:1282\u20139.","journal-title":"Clin Chem"},{"key":"1928_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-019-1235-8","volume":"21","author":"D Fernandez-Garcia","year":"2019","unstructured":"Fernandez-Garcia D, Hills A, Page K, Hastings RK, Toghill B, Goddard KS, et al. Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer. Breast Cancer Res. 2019;21:149.","journal-title":"Breast Cancer Res"},{"key":"1928_CR15","doi-asserted-by":"publisher","first-page":"e103918","DOI":"10.1371\/journal.pone.0103918","volume":"9","author":"S Grisanti","year":"2014","unstructured":"Grisanti S, Almici C, Consoli F, Buglione M, Verardi R, Bolzoni-Villaret A, et al. Circulating tumor cells in patients with recurrent or metastatic head and neck carcinoma: prognostic and predictive significance. PLoS One. 2014;9:e103918.","journal-title":"PLoS One"},{"key":"1928_CR16","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1097\/FTD.0000000000000566","volume":"41","author":"M Oellerich","year":"2019","unstructured":"Oellerich M, Sch\u00fctz E, Beck J, Walson PD. Circulating cell-free DNA-diagnostic and prognostic applications in personalized cancer therapy. Ther Drug Monit. 2019;41:115\u201320.","journal-title":"Ther Drug Monit"},{"key":"1928_CR17","doi-asserted-by":"publisher","first-page":"42008","DOI":"10.18632\/oncotarget.5788","volume":"6","author":"ES Gray","year":"2015","unstructured":"Gray ES, Rizos H, Reid AL, Boyd SC, Pereira MR, Lo J, et al. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015;6:42008\u201318.","journal-title":"Oncotarget."},{"key":"1928_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04001-5","volume":"9","author":"S Manier","year":"2018","unstructured":"Manier S, Park J, Capelletti M, Bustoros M, Freeman SS, Ha G, et al. Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma. Nat Commun. 2018;9:1691.","journal-title":"Nat Commun"},{"key":"1928_CR19","unstructured":"Lee S-Y, Chae D-K, An J, Jung S, Chae CH, Bhak J, et al. Comprehensive mutation profiling of both cfDNA and CTCs in gynecological cancer patients. bioRxiv. 2019:566786."},{"key":"1928_CR20","doi-asserted-by":"publisher","first-page":"224ra24","DOI":"10.1126\/scitranslmed.3007094","volume":"6","author":"C Bettegowda","year":"2014","unstructured":"Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6:224ra24.","journal-title":"Sci Transl Med"},{"key":"1928_CR21","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1158\/2159-8290.CD-13-1014","volume":"4","author":"DA Haber","year":"2014","unstructured":"Haber DA, Velculescu VE. Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Disco. 2014;4:650\u201361.","journal-title":"Cancer Disco"},{"key":"1928_CR22","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646\u201374.","journal-title":"Cell."},{"key":"1928_CR23","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1373\/clinchem.2015.242453","volume":"61","author":"MB Freidin","year":"2015","unstructured":"Freidin MB, Freydina DV, Leung M, Montero Fernandez A, Nicholson AG, Lim E. Circulating tumor DNA outperforms circulating tumor cells for KRAS mutation detection in thoracic malignancies. Clin Chem. 2015;61:1299\u2013304.","journal-title":"Clin Chem"},{"key":"1928_CR24","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1056\/NEJMoa1213261","volume":"368","author":"SJ Dawson","year":"2013","unstructured":"Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013;368:1199\u2013209.","journal-title":"N Engl J Med"},{"key":"1928_CR25","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nrc.2018.11","volume":"18","author":"CR Leemans","year":"2018","unstructured":"Leemans CR, Snijders PJF, Brakenhoff RH. The molecular landscape of head and neck cancer. Nat Rev Cancer. 2018;18:269\u201382.","journal-title":"Nat Rev Cancer"},{"key":"1928_CR26","doi-asserted-by":"publisher","first-page":"3761","DOI":"10.1002\/cam4.2219","volume":"8","author":"S Liebs","year":"2019","unstructured":"Liebs S, Keilholz U, Kehler I, Schweiger C, Hayb\u00e4ck J, Nonnenmacher A. Detection of mutations in circulating cell-free DNA in relation to disease stage in colorectal cancer. Cancer Med. 2019;8:3761\u20139.","journal-title":"Cancer Med"},{"key":"1928_CR27","doi-asserted-by":"publisher","first-page":"e49843","DOI":"10.1371\/journal.pone.0049843","volume":"7","author":"F Salvianti","year":"2012","unstructured":"Salvianti F, Pinzani P, Verderio P, Ciniselli CM, Massi D, De Giorgi V, et al. Multiparametric analysis of cell-free DNA in melanoma patients. PLoS One. 2012;7:e49843.","journal-title":"PLoS One"},{"key":"1928_CR28","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.oraloncology.2015.12.002","volume":"54","author":"AM Mazurek","year":"2016","unstructured":"Mazurek AM, Rutkowski T, Fiszer-Kierzkowska A, Ma\u0142usecka E, Sk\u0142adowski K. Assessment of the total cfDNA and HPV16\/18 detection in plasma samples of head and neck squamous cell carcinoma patients. Oral Oncol. 2016;54:36\u201341.","journal-title":"Oral Oncol"},{"key":"1928_CR29","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.molonc.2014.12.003","volume":"9","author":"R Lebofsky","year":"2015","unstructured":"Lebofsky R, Decraene C, Bernard V, Kamal M, Blin A, Leroy Q, et al. Circulating tumor DNA as a non-invasive substitute to metastasis biopsy for tumor genotyping and personalized medicine in a prospective trial across all tumor types. Mol Oncol. 2015;9:783\u201390.","journal-title":"Mol Oncol"},{"key":"1928_CR30","doi-asserted-by":"publisher","first-page":"2549","DOI":"10.18632\/oncotarget.3041","volume":"6","author":"E Kidess","year":"2015","unstructured":"Kidess E, Heirich K, Wiggin M, Vysotskaia V, Visser BC, Marziali A, et al. Mutation profiling of tumor DNA from plasma and tumor tissue of colorectal cancer patients with a novel, high-sensitivity multiplexed mutation detection platform. Oncotarget. 2015;6:2549\u201361.","journal-title":"Oncotarget."},{"key":"1928_CR31","first-page":"1","volume":"2","author":"SY Lin","year":"2018","unstructured":"Lin SY, Huang SK, Huynh KT, Salomon MP, Chang S-C, Marzese DM, et al. Multiplex gene profiling of cell-free DNA in patients with metastatic melanoma for monitoring disease. JCO Precis Oncol. 2018;2:1\u201330.","journal-title":"JCO Precis Oncol."},{"key":"1928_CR32","doi-asserted-by":"publisher","first-page":"104631","DOI":"10.1016\/j.oraloncology.2020.104631","volume":"104","author":"R Galot","year":"2020","unstructured":"Galot R, van Marcke C, Helaers R, Mendola A, Goebbels RM, Caignet X, et al. Liquid biopsy for mutational profiling of locoregional recurrent and\/or metastatic head and neck squamous cell carcinoma. Oral Oncol. 2020;104:104631.","journal-title":"Oral Oncol"},{"key":"1928_CR33","doi-asserted-by":"publisher","first-page":"293ra104","DOI":"10.1126\/scitranslmed.aaa8507","volume":"7","author":"Y Wang","year":"2015","unstructured":"Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, et al. Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med. 2015;7:293ra104.","journal-title":"Sci Transl Med"},{"key":"1928_CR34","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1093\/annonc\/mdr130","volume":"22","author":"T Hristozova","year":"2011","unstructured":"Hristozova T, Konschak R, Stromberger C, Fusi A, Liu Z, Weichert W, et al. The presence of circulating tumor cells (CTCs) correlates with lymph node metastasis in nonresectable squamous cell carcinoma of the head and neck region (SCCHN). Ann Oncol. 2011;22:1878\u201385.","journal-title":"Ann Oncol"},{"key":"1928_CR35","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1038\/jid.2012.468","volume":"133","author":"L Khoja","year":"2013","unstructured":"Khoja L, Lorigan P, Zhou C, Lancashire M, Booth J, Cummings J, et al. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma. J Invest Dermatol. 2013;133:1582\u201390.","journal-title":"J Invest Dermatol"},{"key":"1928_CR36","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3390\/cells8070755","volume":"8","author":"L Cayrefourcq","year":"2019","unstructured":"Cayrefourcq L, De Roeck A, Garcia C, Stoebner P-E, Fichel F, Garima F, et al. S100-EPISPOT: a new tool to detect viable circulating melanoma cells. Cells. 2019;8:755.","journal-title":"Cells."},{"key":"1928_CR37","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1200\/JCO.2007.15.8923","volume":"26","author":"SJ Cohen","year":"2008","unstructured":"Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3213\u201321.","journal-title":"J Clin Oncol"},{"key":"1928_CR38","doi-asserted-by":"crossref","unstructured":"Genna A, Vanwynsberghe AM, Villard AV, Pottier C, Ancel J, Polette M, et al. EMT-associated heterogeneity in circulating tumor cells: sticky friends on the road to metastasis. Cancers (Basel). 2020;12:1632.","DOI":"10.3390\/cancers12061632"},{"key":"1928_CR39","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1126\/science.1228522","volume":"339","author":"M Yu","year":"2013","unstructured":"Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339:580\u20134.","journal-title":"Science."},{"key":"1928_CR40","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.molonc.2014.12.001","volume":"9","author":"M Pestrin","year":"2015","unstructured":"Pestrin M, Salvianti F, Galardi F, De Luca F, Turner N, Malorni L, et al. Heterogeneity of PIK3CA mutational status at the single cell level in circulating tumor cells from metastatic breast cancer patients. Mol Oncol. 2015;9:749\u201357.","journal-title":"Mol Oncol"},{"key":"1928_CR41","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1093\/annonc\/mdv165","volume":"26","author":"E Pailler","year":"2015","unstructured":"Pailler E, Auger N, Lindsay CR, Vielh P, Islas-Morris-Hernandez A, Borget I, et al. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer. Ann Oncol. 2015;26:1408\u201315.","journal-title":"Ann Oncol"},{"key":"1928_CR42","doi-asserted-by":"publisher","first-page":"26107","DOI":"10.18632\/oncotarget.8431","volume":"7","author":"F De Luca","year":"2016","unstructured":"De Luca F, Rotunno G, Salvianti F, Galardi F, Pestrin M, Gabellini S, et al. Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer. Oncotarget. 2016;7:26107\u201319.","journal-title":"Oncotarget."},{"key":"1928_CR43","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-020-01447-w","volume":"38","author":"J Majidpoor","year":"2021","unstructured":"Majidpoor J, Mortezaee K. Steps in metastasis: an updated review. Med Oncol. 2021;38:3.","journal-title":"Med Oncol"},{"key":"1928_CR44","doi-asserted-by":"publisher","first-page":"2686","DOI":"10.1002\/cam4.2871","volume":"9","author":"B Hu","year":"2020","unstructured":"Hu B, Tian X, Li Y, Liu Y, Yang T, Han Z, et al. Epithelial-mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1. Cancer Med. 2020;9:2686\u201397.","journal-title":"Cancer Med"},{"key":"1928_CR45","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1126\/science.aab0917","volume":"349","author":"DT Miyamoto","year":"2015","unstructured":"Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT, et al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science. 2015;349:1351\u20136.","journal-title":"Science."},{"key":"1928_CR46","doi-asserted-by":"crossref","unstructured":"Gorges K, Wiltfang L, Gorges TM, Sartori A, Hildebrandt L, Keller L, et al. Intra-patient heterogeneity of circulating tumor cells and circulating tumor DNA in blood of melanoma patients. Cancers (Basel). 2019;11:1685.","DOI":"10.3390\/cancers11111685"},{"key":"1928_CR47","doi-asserted-by":"crossref","unstructured":"Yap SA, M\u00fcnster-Wandowski A, Nonnenmacher A, Keilholz U, Liebs S. Analysis of cancer-related mutations in extracellular vesicles RNA by Droplet Digital\u2122 PCR. Biotechniques. 2020;69:99\u2013107.","DOI":"10.2144\/btn-2020-0028"},{"key":"1928_CR48","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1111\/cas.14092","volume":"110","author":"K Onidani","year":"2019","unstructured":"Onidani K, Shoji H, Kakizaki T, Yoshimoto S, Okaya S, Miura N, et al. Monitoring of cancer patients via next-generation sequencing of patient-derived circulating tumor cells and tumor DNA. Cancer Sci. 2019;110:2590\u20139.","journal-title":"Cancer Sci"},{"key":"1928_CR49","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1138-3","volume":"15","author":"J Lack","year":"2017","unstructured":"Lack J, Gillard M, Cam M, Paner GP, VanderWeele DJ. Circulating tumor cells capture disease evolution in advanced prostate cancer. J Transl Med. 2017;15:44.","journal-title":"J Transl Med"},{"key":"1928_CR50","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ejca.2019.04.015","volume":"116","author":"T Eder","year":"2019","unstructured":"Eder T, Hess AK, Konschak R, Stromberger C, Johrens K, Fleischer V, et al. Interference of tumour mutational burden with outcome of patients with head and neck cancer treated with definitive chemoradiation: a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group. Eur J Cancer. 2019;116:67\u201376.","journal-title":"Eur J Cancer"},{"key":"1928_CR51","doi-asserted-by":"publisher","first-page":"D941","DOI":"10.1093\/nar\/gky1015","volume":"47","author":"JG Tate","year":"2019","unstructured":"Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, et al. COSMIC: the catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47:D941\u2013d7.","journal-title":"Nucleic Acids Res"},{"key":"1928_CR52","unstructured":"COSMIC \u2013 Catalogue of somatic mutations in cancer. cancer.sanger.ac.uk. 2004. accessed date 17.07.2019."},{"key":"1928_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0531-8","volume":"10","author":"D Tamborero","year":"2018","unstructured":"Tamborero D, Rubio-Perez C, Deu-Pons J, Schroeder MP, Vivancos A, Rovira A, et al. Cancer Genome Interpreter annotates the biological and clinical relevance of tumor alterations. Genome Med. 2018;10:25.","journal-title":"Genome Med"},{"key":"1928_CR54","unstructured":"Institute for Research in Biomedicine. Cancer Genome Interpreter. 2018. accessed date 17.07.2019. https:\/\/www.cancergenomeinterpreter.org."}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01928-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01928-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01928-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:07:23Z","timestamp":1629364043000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-021-01928-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,6]]},"references-count":54,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2021,8,19]]}},"alternative-id":["1928"],"URL":"https:\/\/doi.org\/10.1038\/s41388-021-01928-w","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,6]]},"assertion":[{"value":"22 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests. MS is an employee of Alacris Theranostics GmbH.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}