Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression.
Int J Mol Sci
; 21(4)2020 Feb 21.
Article
in En
| MEDLINE
| ID: mdl-32098246
ABSTRACT
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% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Chromosomes, Human, Pair 9
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Carcinoma, Renal Cell
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Biomarkers, Tumor
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Chromosome Deletion
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Single-Cell Analysis
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Kidney Neoplasms
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Neoplastic Cells, Circulating
Type of study:
Clinical_trials
Limits:
Female
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Humans
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Male
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Middle aged
Language:
En
Year:
2020
Type:
Article