Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression.

Vera Cappelletti, Elena Verzoni, Raffaele Ratta, Marta Vismara, Marco Silvestri, Rosanna Montone, Patrizia Miodini, Carolina Reduzzi, Melanie Claps, Pierangela Sepe, Maria Grazia Daidone, Giuseppe Procopio

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Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28 62 and 71 progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - Feb 1 2020


  • Female
  • Humans
  • Male
  • Middle Aged
  • copy number alterations
  • cancer evolution
  • circulating tumor cells
  • heterogeneity
  • renal cell cancer
  • single-cell analysis
  • *Biomarkers
  • Tumor/genetics/metabolism
  • *Carcinoma
  • Renal Cell/genetics/metabolism/pathology
  • *Chromosome Deletion
  • *Kidney Neoplasms/genetics/metabolism/pathology
  • *Neoplastic Cells
  • Circulating/metabolism/pathology
  • *Single-Cell Analysis
  • Chromosomes
  • Human
  • Pair 9/*genetics
  • High-Throughput Nucleotide Sequencing


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