Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs captured by a label-free platform: Comparison to ctDNA and tissue in metastatic colorectal cancer.
Oncotarget
; 7(51): 85349-85364, 2016 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-27863403
ABSTRACT
Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers, including CTCs and ctDNA, hold promise for evaluating treatment response in real-time and guiding therapeutic modifications. From 15 patients with advanced CRC undergoing liver metastasectomy with curative intent, we collected 41 blood samples at different time points before and after surgery for CTC isolation and quantification using label-free Vortex technology. For mutational profiling, KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23 samples, nine matched liver metastases and three primary tumor samples. Mutational patterns were compared. 80% of patient blood samples were positive for CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of 78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases, CTCs exhibited a mutation that was not detected in ctDNA, and vice versa. Complementary assessment of both CTCs and ctDNA appears advantageous to assess dynamic tumor profiles.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Colon_e_reto
Base de dados:
MEDLINE
Assunto principal:
Análise Mutacional de DNA
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Neoplasias Colorretais
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Biomarcadores Tumorais
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Proteínas Proto-Oncogênicas p21(ras)
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Proteínas Proto-Oncogênicas B-raf
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Classe I de Fosfatidilinositol 3-Quinases
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DNA Tumoral Circulante
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Mutação
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Células Neoplásicas Circulantes
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Oncotarget
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha