PheoSeq: A Targeted Next-Generation Sequencing Assay for Pheochromocytoma and Paraganglioma Diagnostics.

Genetic diagnosis is recommended for all pheochromocytoma and paraganglioma (PPGL) cases, as driver mutations are identified in approximately 80% of the cases. As the list of related genes expands, genetic diagnosis becomes more time-consuming, and targeted next-generation sequencing (NGS) has emerg...

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Detalles Bibliográficos
Autores: Currás-Freixes, Maria, Piñeiro-Yañez, Elena, Montero-Conde, Cristina, Apellániz-Ruiz, María, Calsina, Bruna, Mancikova, Veronika, Remacha, Laura, Richter, Susan, Ercolino, Tonino, Rogowski-Lehmann, Natalie, Deutschbein, Timo, Calatayud, María, Guadalix, Sonsoles, Álvarez-Escolá, Cristina, Lamas, Cristina, Aller, Javier, Sastre-Marcos, Julia, Lázaro, Conxi, Galofré, Juan C, Patiño-García, Ana, Meoro-Avilés, Amparo, Balmaña-Gelpi, Judith, De Miguel-Novoa, Paz, Balbín, Milagros, Matías-Guiu, Xavier, Letón, Rocío, Inglada-Pérez, Lucía, Torres-Pérez, Rafael, Roldán-Romero, Juan M, Rodríguez-Antona, Cristina, Fliedner, Stephanie M J, Opocher, Giuseppe, Pacak, Karel, Korpershoek, Esther, de Krijger, Ronald R, Vroonen, Laurent, Mannelli, Massimo, Fassnacht, Martin, Beuschlein, Felix, Eisenhofer, Graeme, Cascón, Alberto, Al-Shahrour, Fatima, Robledo Batanero, Mercedes
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26019
Acceso en línea:https://hdl.handle.net/20.500.12105/26019
Access Level:acceso abierto
Palabra clave:SUCCINATE-DEHYDROGENASE
GERMLINE MUTATIONS
GENE-MUTATIONS
NF1 GENE
MALIGNANT PHEOCHROMOCYTOMAS
PRENATAL-DIAGNOSIS
NECK PARAGANGLIOMA
RET PROTOONCOGENE
HIF2A MUTATIONS
HIGH-FREQUENCY
Descripción
Sumario:Genetic diagnosis is recommended for all pheochromocytoma and paraganglioma (PPGL) cases, as driver mutations are identified in approximately 80% of the cases. As the list of related genes expands, genetic diagnosis becomes more time-consuming, and targeted next-generation sequencing (NGS) has emerged as a cost-effective tool. This study aimed to optimize targeted NGS in PPGL genetic diagnostics. A workflow based on two customized targeted NGS assays was validated to study the 18 main PPGL genes in germline and frozen tumor DNA, with one of them specifically directed toward formalin-fixed paraffin-embedded tissue. The series involved 453 unrelated PPGL patients, of whom 30 had known mutations and were used as controls. Partial screening using Sanger had been performed in 275 patients. NGS results were complemented with the study of gross deletions. NGS assay showed a sensitivity ≥99.4%, regardless of DNA source. We identified 45 variants of unknown significance and 89 pathogenic mutations, the latter being germline in 29 (7.2%) and somatic in 58 (31.7%) of the 183 tumors studied. In 37 patients previously studied by Sanger sequencing, the causal mutation could be identified. We demonstrated that both assays are an efficient and accurate alternative to conventional sequencing. Their application facilitates the study of minor PPGL genes, and enables genetic diagnoses in patients with incongruent or missing clinical data, who would otherwise be missed.

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