Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study

Abstract

Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.

ctDNA predicts clinical T1a to pathological T3a upstaging after partial nephrectomy

“…Sequencing libraries were hybridized with customized probes targeting 16 RCC‐related genes previously developed by our team. 29 The enriched DNA was amplified, and clusters were generated and sequenced on a NovaSeq 6000 System (Illumina) with 2 × 151 bp reads, targeting an average sequencing depth of 35,000× for each sample. All procedures were performed according to the manufacturer's instructions.…”