Plasma cell-free DNA variant analysis compared with methylated DNA analysis in renal cell carcinoma.

Abstract

PURPOSE:

Plasma cell-free DNA (cfDNA) variant analysis is commonly used in many cancer subtypes. Cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) has shown high sensitivity for cancer detection. To date, studies have not compared the sensitivity of both methods in a single cancer subtype.

METHODS:

cfDNA from 40 metastatic RCC (mRCC) patients was subjected to targeted panel variant analysis. For 34 of 40, cfMeDIP-seq was also performed. A separate cohort of 38 mRCC patients were used in cfMeDIP-seq analysis to train an RCC classifier.

RESULTS:

cfDNA variant analysis detected 21 candidate variants in 11 of 40 mRCC patients (28%), after exclusion of 2 germline variants and 6 variants reflecting clonal hematopoiesis. Among 23 patients with parallel tumor sequencing, cfDNA analysis alone identified variants in 9 patients (39%), while cfDNA analysis focused on tumor sequencing variant findings improved the sensitivity to 52%. In 34 mRCC patients undergoing cfMeDIP-seq, cfDNA variant analysis identified variants in 7 (21%), while cfMeDIP-seq detected all mRCC cases (100% sensitivity) with 88% specificity in 34 control subjects. In 5 patients with cfDNA variants and serial samples, variant frequency correlated with response to therapy.

CONCLUSION:

cfMeDIP-seq is significantly more sensitive for mRCC detection than cfDNA variant analysis. However, cfDNA variant analysis may be useful for monitoring response to therapy.

• Authors: Kathryn Lasseter, Amin H Nassar, Lana Hamieh, Jacob E Berchuck, Pier Vitale Nuzzo, Keegan Korthauer, Atul B Shinagare, Barbara Ogorek, Rana McKay, Aaron R Thorner, Gwo-Shu Mary Lee, David A Braun, Rupal S Bhatt, Matthew Freedman, Toni K Choueiri, David J Kwiatkowski
• Journal: Genetics in medicine : official journal of the American College of Medical Genetics (Genet Med) Vol. 22 Issue 8 Pg. 1366-1373 (08 2020) ISSN: 1530-0366 [Electronic] United States
• PMID: 32341571 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Cell-Free Nucleic Acids
• DNA

Topics

• Biomarkers, Tumor (genetics)
• Carcinoma, Renal Cell (diagnosis, genetics)
• Cell-Free Nucleic Acids (genetics)
• DNA
• High-Throughput Nucleotide Sequencing
• Humans
• Kidney Neoplasms (diagnosis, genetics)
• Plasma