Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel

Abstract Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence mul...

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Autores principales:	Blanca de Unamuno Bustos, Rosa Murria Estal, Gema Pérez Simó, Inmaculada de Juan Jimenez, Begoña Escutia Muñoz, Mercedes Rodríguez Serna, Victor Alegre de Miquel, Margarita Llavador Ros, Rosa Ballester Sánchez, Eduardo Nagore Enguídanos, Sarai Palanca Suela, Rafael Botella Estrada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e39afa7edb1547ada0b0f991d05e9aec
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spelling	oai:doaj.org-article:e39afa7edb1547ada0b0f991d05e9aec2021-12-02T11:53:08ZTowards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel10.1038/s41598-017-00606-w2045-2322https://doaj.org/article/e39afa7edb1547ada0b0f991d05e9aec2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00606-whttps://doaj.org/toc/2045-2322Abstract Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.Blanca de Unamuno BustosRosa Murria EstalGema Pérez SimóInmaculada de Juan JimenezBegoña Escutia MuñozMercedes Rodríguez SernaVictor Alegre de MiquelMargarita Llavador RosRosa Ballester SánchezEduardo Nagore EnguídanosSarai Palanca SuelaRafael Botella EstradaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Blanca de Unamuno Bustos Rosa Murria Estal Gema Pérez Simó Inmaculada de Juan Jimenez Begoña Escutia Muñoz Mercedes Rodríguez Serna Victor Alegre de Miquel Margarita Llavador Ros Rosa Ballester Sánchez Eduardo Nagore Enguídanos Sarai Palanca Suela Rafael Botella Estrada Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
description	Abstract Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.
format	article
author	Blanca de Unamuno Bustos Rosa Murria Estal Gema Pérez Simó Inmaculada de Juan Jimenez Begoña Escutia Muñoz Mercedes Rodríguez Serna Victor Alegre de Miquel Margarita Llavador Ros Rosa Ballester Sánchez Eduardo Nagore Enguídanos Sarai Palanca Suela Rafael Botella Estrada
author_facet	Blanca de Unamuno Bustos Rosa Murria Estal Gema Pérez Simó Inmaculada de Juan Jimenez Begoña Escutia Muñoz Mercedes Rodríguez Serna Victor Alegre de Miquel Margarita Llavador Ros Rosa Ballester Sánchez Eduardo Nagore Enguídanos Sarai Palanca Suela Rafael Botella Estrada
author_sort	Blanca de Unamuno Bustos
title	Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
title_short	Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
title_full	Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
title_fullStr	Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
title_full_unstemmed	Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel
title_sort	towards personalized medicine in melanoma: implementation of a clinical next-generation sequencing panel
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e39afa7edb1547ada0b0f991d05e9aec
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Towards Personalized Medicine in Melanoma: Implementation of a Clinical Next-Generation Sequencing Panel

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