Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma

Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kate I. Glennon, Mahafarin Maralani, Narges Abdian, Antoine Paccard, Laura Montermini, Alice Jisoo Nam, Madeleine Arseneault, Alfredo Staffa, Pouria Jandaghi, Brian Meehan, Fadi Brimo, Simon Tanguay, Janusz Rak, Yasser Riazalhosseini
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	renal cell carcinoma liquid biopsy NGS cfDNA ctDNA extracellular vesicles Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e16a1ef71eb64074ade75295117b9a5a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e16a1ef71eb64074ade75295117b9a5a
record_format	dspace
spelling	oai:doaj.org-article:e16a1ef71eb64074ade75295117b9a5a2021-11-25T17:04:27ZRational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma10.3390/cancers132258252072-6694https://doaj.org/article/e16a1ef71eb64074ade75295117b9a5a2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5825https://doaj.org/toc/2072-6694Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.Kate I. GlennonMahafarin MaralaniNarges AbdianAntoine PaccardLaura MonterminiAlice Jisoo NamMadeleine ArseneaultAlfredo StaffaPouria JandaghiBrian MeehanFadi BrimoSimon TanguayJanusz RakYasser RiazalhosseiniMDPI AGarticlerenal cell carcinomaliquid biopsyNGScfDNActDNAextracellular vesiclesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5825, p 5825 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	renal cell carcinoma liquid biopsy NGS cfDNA ctDNA extracellular vesicles Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	renal cell carcinoma liquid biopsy NGS cfDNA ctDNA extracellular vesicles Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kate I. Glennon Mahafarin Maralani Narges Abdian Antoine Paccard Laura Montermini Alice Jisoo Nam Madeleine Arseneault Alfredo Staffa Pouria Jandaghi Brian Meehan Fadi Brimo Simon Tanguay Janusz Rak Yasser Riazalhosseini Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
description	Renal cell carcinoma (RCC) is known for its variable clinical behavior and outcome, including heterogeneity in developing relapse or metastasis. Recent data highlighted the potential of somatic mutations as promising biomarkers for risk stratification in RCC. Likewise, the analysis of circulating tumor DNA (ctDNA) for such informative somatic mutations (liquid biopsy) is considered an important advance for precision oncology in RCC, allowing to monitor molecular disease evolution in real time. However, our knowledge about the utility of ctDNA analysis in RCC is limited, in part due to the lack of RCC-appropriate assays for ctDNA analysis. Here, by interrogating different blood compartments in xenograft models, we identified plasma cell-free (cf) DNA and extracellular vesicles (ev) DNA enriched for RCC-associated ctDNA. Additionally, we developed sensitive targeted sequencing and bioinformatics workflows capable of detecting somatic mutations in RCC-relevant genes with allele frequencies ≥ 0.5%. Applying this assay to patient-matched tumor and liquid biopsies, we captured tumor mutations in cf- and ev-DNA fractions isolated from the blood, highlighting the potentials of both fractions for ctDNA analysis. Overall, our study presents an RCC-appropriate sequencing assay and workflow for ctDNA analysis and provides a proof of principle as to the feasibility of detecting tumor-specific mutations in liquid biopsy in RCC patients.
format	article
author	Kate I. Glennon Mahafarin Maralani Narges Abdian Antoine Paccard Laura Montermini Alice Jisoo Nam Madeleine Arseneault Alfredo Staffa Pouria Jandaghi Brian Meehan Fadi Brimo Simon Tanguay Janusz Rak Yasser Riazalhosseini
author_facet	Kate I. Glennon Mahafarin Maralani Narges Abdian Antoine Paccard Laura Montermini Alice Jisoo Nam Madeleine Arseneault Alfredo Staffa Pouria Jandaghi Brian Meehan Fadi Brimo Simon Tanguay Janusz Rak Yasser Riazalhosseini
author_sort	Kate I. Glennon
title	Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
title_short	Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
title_full	Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
title_fullStr	Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
title_full_unstemmed	Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma
title_sort	rational development of liquid biopsy analysis in renal cell carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e16a1ef71eb64074ade75295117b9a5a
work_keys_str_mv	AT kateiglennon rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT mahafarinmaralani rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT nargesabdian rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT antoinepaccard rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT lauramontermini rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT alicejisoonam rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT madeleinearseneault rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT alfredostaffa rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT pouriajandaghi rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT brianmeehan rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT fadibrimo rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT simontanguay rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT januszrak rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma AT yasserriazalhosseini rationaldevelopmentofliquidbiopsyanalysisinrenalcellcarcinoma
_version_	1718412746910859264

Rational Development of Liquid Biopsy Analysis in Renal Cell Carcinoma

Ejemplares similares