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Open AccessArticle

Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice

1
Department of Medicine, Kansas City School of Medicine, University of Missouri, Kansas City, MO 64110, USA
2
Division of Hematology/Oncology and Cell Therapy, Rush University Medical Center, Chicago, IL 60612, USA
3
Division of Oncology, Saint Luke’s Cancer Institute, Kansas City, MO 64111, USA
4
Rush Precision Oncology Program, Rush University Medical Center, Chicago, IL 60612, USA
5
Division of Surgical Oncology, Rush University Medical Center, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(9), 1399; https://doi.org/10.3390/cancers11091399
Received: 29 July 2019 / Revised: 4 September 2019 / Accepted: 7 September 2019 / Published: 19 September 2019
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
Tumor heterogeneity, especially intratumoral heterogeneity, is a primary reason for treatment failure. A single biopsy may not reflect the complete genomic architecture of the tumor needed to make therapeutic decisions. Circulating tumor DNA (ctDNA) is believed to overcome these limitations. We analyzed concordance between ctDNA and whole-exome sequencing/whole-genome sequencing (WES/WGS) of tumor samples from patients with breast (n = 12), gastrointestinal (n = 20), lung (n = 19), and other tumor types (n = 13). Correlation in the driver, hotspot, and actionable alterations was studied. Three cases in which more-in-depth genomic analysis was required have been presented. A total 58% (37/64) of patients had at least one concordant mutation. Patients who had received systemic therapy before tissue next-generation sequencing (NGS) and ctDNA analysis showed high concordance (78% (21/27) vs. 43% (12/28) p = 0.01, respectively). Obtaining both NGS and ctDNA increased actionable alterations from 28% (18/64) to 52% (33/64) in our patients. Twenty-one patients had mutually exclusive actionable alterations seen only in either tissue NGS or ctDNA samples. Somatic hotspot mutation analysis showed significant discordance between tissue NGS and ctDNA analysis, denoting significant tumor heterogeneity in these malignancies. Increased tissue tumor mutation burden (TMB) positively correlated with the number of ctDNA mutations in patients who had received systemic therapy, but not in treatment-naïve patients. Prior systemic therapy and TMB may affect concordance and should be taken into consideration in future studies. Incorporating driver, actionable, and hotspot analysis may help to further refine the correlation between these two platforms. Tissue NGS and ctDNA are complimentary, and if done in conjunction, may increase the detection rate of actionable alterations and potentially therapeutic targets. View Full-Text
Keywords: circulating tumor DNA; next generation sequencing; driver alterations; actionable alterations; concordance circulating tumor DNA; next generation sequencing; driver alterations; actionable alterations; concordance
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MDPI and ACS Style

Imperial, R.; Nazer, M.; Ahmed, Z.; Kam, A.E.; Pluard, T.J.; Bahaj, W.; Levy, M.; Kuzel, T.M.; Hayden, D.M.; Pappas, S.G.; Subramanian, J.; Masood, A. Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice. Cancers 2019, 11, 1399.

AMA Style

Imperial R, Nazer M, Ahmed Z, Kam AE, Pluard TJ, Bahaj W, Levy M, Kuzel TM, Hayden DM, Pappas SG, Subramanian J, Masood A. Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice. Cancers. 2019; 11(9):1399.

Chicago/Turabian Style

Imperial, Robin; Nazer, Marjan; Ahmed, Zaheer; Kam, Audrey E.; Pluard, Timothy J.; Bahaj, Waled; Levy, Mia; Kuzel, Timothy M.; Hayden, Dana M.; Pappas, Sam G.; Subramanian, Janakiraman; Masood, Ashiq. 2019. "Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice" Cancers 11, no. 9: 1399.

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