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Article

TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation

1
Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
2
Genomic Epidemiology Branch, International Agency for Research on Cancer/World Health Organization (IARC/WHO), 69000 Lyon, France
3
Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49177-44563, Iran
4
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08036 Barcelona, Spain
5
Institute for Advanced Biosciences, Inserm 1209 CNRS 5309 UGA, 38700 Grenoble, France
*
Author to whom correspondence should be addressed.
Academic Editors: Ines Gockel and Asfar S. Azmi
Int. J. Mol. Sci. 2021, 22(11), 5627; https://doi.org/10.3390/ijms22115627
Received: 7 April 2021 / Revised: 28 April 2021 / Accepted: 17 May 2021 / Published: 26 May 2021
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., >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 (1.11–3.29)), 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. View Full-Text
Keywords: circulating cell-free DNA; liquid biopsy; circulating tumor DNA; esophageal squamous cell carcinoma; TP53; tumor mutation; variant caller; deep sequencing; neoantigen circulating cell-free DNA; liquid biopsy; circulating tumor DNA; esophageal squamous cell carcinoma; TP53; tumor mutation; variant caller; deep sequencing; neoantigen
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MDPI and ACS Style

Nasrollahzadeh, D.; Roshandel, G.; Delhomme, T.M.; Avogbe, P.H.; Foll, M.; Saidi, F.; Poustchi, H.; Sotoudeh, M.; Malekzadeh, R.; Brennan, P.; Mckay, J.; Hainaut, P.; Abedi-Ardekani, B. TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation. Int. J. Mol. Sci. 2021, 22, 5627. https://doi.org/10.3390/ijms22115627

AMA Style

Nasrollahzadeh D, Roshandel G, Delhomme TM, Avogbe PH, Foll M, Saidi F, Poustchi H, Sotoudeh M, Malekzadeh R, Brennan P, Mckay J, Hainaut P, Abedi-Ardekani B. TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation. International Journal of Molecular Sciences. 2021; 22(11):5627. https://doi.org/10.3390/ijms22115627

Chicago/Turabian Style

Nasrollahzadeh, Dariush, Gholamreza Roshandel, Tiffany M. Delhomme, Patrice H. Avogbe, Matthieu Foll, Farrokh Saidi, Hossein Poustchi, Masoud Sotoudeh, Reza Malekzadeh, Paul Brennan, James Mckay, Pierre Hainaut, and Behnoush Abedi-Ardekani. 2021. "TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation" International Journal of Molecular Sciences 22, no. 11: 5627. https://doi.org/10.3390/ijms22115627

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