MP03-09 CIRCULATING TUMOR DNA AS A BIOMARKER IN ADVANCED RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I1 Apr 2016MP03-09 CIRCULATING TUMOR DNA AS A BIOMARKER IN ADVANCED RENAL CELL CARCINOMA Mark Ball, Michael Gorin, Gunes Gunters, Phillip Pierorazio, George Netto, Channing Paller, Hans Hammers, Luis Diaz, and Mohamad Allaf Mark BallMark Ball More articles by this author , Michael GorinMichael Gorin More articles by this author , Gunes GuntersGunes Gunters More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , George NettoGeorge Netto More articles by this author , Channing PallerChanning Paller More articles by this author , Hans HammersHans Hammers More articles by this author , Luis DiazLuis Diaz More articles by this author , and Mohamad AllafMohamad Allaf More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1902AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There are currently no serum biomarkers for renal cell carcinoma (RCC). Circulating tumor DNA (ctDNA) has been shown to correlate with advanced disease and response to therapy in several solid malignancies; however little is known about the presence of ctDNA in patients with RCC. We sough to characterize the presence of ctDNA in patients with locally advanced and metastatic RCC. METHODS Pre-operative serum was collected from 4 patients with locally advanced (>T3b) (n=2) or metastatic (n=2) clear cell RCC. DNA from fresh-frozen paraffin-embedded (FFPE) nephrectomy specimens was isolated, and a next-generation sequencing assay to identify somatic mutations in 300 cancer-associated genes was used to determine tissue mutations. One high allele frequency mutation was selected for each sample. Primers for these mutations were constructed for digital PCR of matched serum specimens. Patients with positive pretreatment ctDNA were followed longitudinally to assess changes in ctDNA levels with treatment. RESULTS Next generation sequencing identified known mutations in all 4 tumors specimens. Candidate mutations selected were from the following genes: VHL, BAP1, PBRM1, NF. Serum PCR failed to detect mutant alleles in either locally advanced case, but ctDNA was detected in 1 metastatic patient with substitution mutation resulting in a splice site donor of VHL. In this patient, ctDNA burden decreased after nephrectomy and initiation of systemic therapy, but increased with disease progression (Figure 1). CONCLUSIONS In this pilot study, ctDNA was detected in 1 of 4 patients. In patients with detectable ctDNA at baseline, ctDNA dynamics may correlate with tumor burden. Future directions will work to optimize the detection of ctDNA in patients with metastatic RCC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e22 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Mark Ball More articles by this author Michael Gorin More articles by this author Gunes Gunters More articles by this author Phillip Pierorazio More articles by this author George Netto More articles by this author Channing Paller More articles by this author Hans Hammers More articles by this author Luis Diaz More articles by this author Mohamad Allaf More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...