{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T23:51:15Z","timestamp":1782604275686,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012155","name":"National Institute for Medical Research Development","doi-asserted-by":"publisher","award":["977009"],"award-info":[{"award-number":["977009"]}],"id":[{"id":"10.13039\/501100012155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CRUK grand challenge","award":["JVA31108425-1"],"award-info":[{"award-number":["JVA31108425-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., &gt;1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11\u20133.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.<\/jats:p>","DOI":"10.3390\/ijms22115627","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T10:30:32Z","timestamp":1622025032000},"page":"5627","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation"],"prefix":"10.3390","volume":"22","author":[{"given":"Dariush","family":"Nasrollahzadeh","sequence":"first","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran"},{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gholamreza","family":"Roshandel","sequence":"additional","affiliation":[{"name":"Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49177-44563, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0265-4246","authenticated-orcid":false,"given":"Tiffany Myriam","family":"Delhomme","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"},{"name":"Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice Hodonou","family":"Avogbe","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-8436","authenticated-orcid":false,"given":"Matthieu","family":"Foll","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrokh","family":"Saidi","sequence":"additional","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Poustchi","sequence":"additional","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-4150","authenticated-orcid":false,"given":"Masoud","family":"Sotoudeh","sequence":"additional","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-6335","authenticated-orcid":false,"given":"Reza","family":"Malekzadeh","sequence":"additional","affiliation":[{"name":"Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brennan","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Mckay","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Hainaut","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Inserm 1209 CNRS 5309 UGA, 38700 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0980-0587","authenticated-orcid":false,"given":"Behnoush","family":"Abedi-Ardekani","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer\/World Health Organization (IARC\/WHO), 69000 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1200\/JCO.2017.76.8671","article-title":"Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review","volume":"36","author":"Merker","year":"2018","journal-title":"J. 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