Research Papers:

Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications

Andrew W. Hahn, David M. Gill, Benjamin Maughan, Archana Agarwal, Lubina Arjyal, Sumati Gupta, Jessica Streeter, Erin Bailey, Sumanta K. Pal and Neeraj Agarwal _

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Oncotarget. 2017; 8:33614-33620. https://doi.org/10.18632/oncotarget.16833

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Andrew W. Hahn1, David M. Gill1, Benjamin Maughan2, Archana Agarwal3, Lubina Arjyal2, Sumati Gupta2, Jessica Streeter4, Erin Bailey4, Sumanta K. Pal5, Neeraj Agarwal2

1Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

2Division of Medical Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA

3Department of Pathology, University of Utah, Salt Lake City, UT, USA

4Department of Pharmacy, Huntsman Cancer Institute, Salt Lake City, UT, USA

5Department of Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA

Correspondence to:

Neeraj Agarwal, email: [email protected]

Keywords: circulating tumor DNA NGS, tumor tissue NGS, correlation, metastatic renal cell carcinoma

Received: January 25, 2017     Accepted: March 25, 2017     Published: April 04, 2017


Introduction: Tumor tissue and circulating tumor DNA (ctDNA) next-generation sequencing (NGS) testing are frequently performed to detect genomic alterations (GAs) to help guide treatment in metastatic renal cell carcinoma (mRCC), especially after progression on standard systemic therapy. Our objective was to assess if GAs detected by ctDNA NGS are different from those detected by tumor tissue NGS, specifically in patients with mRCC, and if these platforms are interchangeable or complimentary.

Results: When controlling for genes tested by both platforms, the median mutation rate for ctDNA was similar to tissue (median 3.0 vs. 1.0, p = 0.14). However, the concordance rate between the two platforms was only 8.6%. When comparing GAs by molecular pathway, GAs in tumor tissue were more common for the DNA repair and epigenetic pathways.

Materials and Methods: Results of NGS testing from tumor tissue and ctDNA from 19 sequential mRCC patients were compared. GAs in each were statistically evaluated using the Wilcoxon signed-rank test. The Fischer’s exact test was used to compare the incidence of mutations in selected molecular pathways.

Conclusions: When controlling for genes tested by both platforms, similar number of GAs were detected by both tissue and ctDNA based NGS. However, there was discordance in the type of GAs detected suggesting that ctDNA NGS may be more reflective of dynamic tumor genomic heterogeneity. Hence, these two platforms may be considered complementary to each other, rather than interchangeable, for assessment of tumor GAs to guide selection of targeted clinical trial therapies.

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