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

Fecha de publicación: 29/03/2017

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

Alegre de Miquel V
Ballester Sánchez R
Nagore Enguídanos E

Grupos

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 >= 500x. 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.

Datos de la publicación

ISSN/ISSNe:: 2045-2322, 2045-2322
Tipo:: Article
Páginas:: 495-495
DOI:: 10.1038/s41598-017-00606-w
Factor de Impacto:: 1,533 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

de Unamuno Bustos B:: Department of Dermatology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Murria Estal R:: Molecular Biology Laboratory, Service of Clinical Analysis, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Pérez Simó G:: Molecular Biology Laboratory, Service of Clinical Analysis, Hospital Universitari i Politecnic La Fe, Valencia, Spain
de Juan Jimenez I:: Molecular Biology Laboratory, Service of Clinical Analysis, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Escutia Muñoz B:: Department of Dermatology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Rodríguez Serna M:: Department of Dermatology, Hospital Universitari i Politecnic La Fe, Valencia, Spain
Alegre de Miquel V:: Department of Dermatology, Hospital General Universitario de Valencia, Valencia, Spain
Llavador Ros M:: Department of Pathology, Hospital Universitari i Politècnic la Fe, Valencia, Spain
Ballester Sánchez R:: Department of Dermatology, La Plana Hospital, Villarreal, Castellón, Spain
Nagore Enguídanos E:: Department of Dermatology, Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain
Palanca Suela S:: Molecular Biology Laboratory, Service of Clinical Analysis, Hospital Universitari i Politecnic La Fe, Valencia, Spain.
Botella Estrada R:: Department of Dermatology, Hospital Universitari i Politecnic La Fe, Valencia, Spain