Publicaciones científicas

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

Currás-Freixes M (1), Piñeiro-Yañez E (2), Montero-Conde C (1), Apellániz-Ruiz M (1), Calsina B (1), Mancikova V (1), Remacha L (1), Richter S (3), Ercolino T (4), Rogowski-Lehmann N (5), Deutschbein T (6), Calatayud M (7), Guadalix S (7), Álvarez-Escolá C (8), Lamas C (9), Aller J (10), Sastre-Marcos J (11), Lázaro C (12), Galofré JC (13), Patiño-García A (14), Meoro-Avilés A (15), Balmaña-Gelpi J (16), De Miguel-Novoa P (17), Balbín M (18), Matías-Guiu X (19), Letón R (1), Inglada-Pérez L (20), Torres-Pérez R (1), Roldán-Romero JM (1), Rodríguez-Antona C (20), Fliedner SMJ (21), Opocher G (22), Pacak K (23), Korpershoek E (24), de Krijger RR (25), Vroonen L (26), Mannelli M (4), Fassnacht M (6), Beuschlein F (5), Eisenhofer G (27), Cascón A (20), Al-Shahrour F (2), Robledo M (28). (1) Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
(2) Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
(3) Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany.
(4) Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence and Istituto Toscano Tumori, Florence, Italy.
(5) Department of Internal Medicine IV Campus Innenstadt, University-Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany.
(6) Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany.
(7) Department of Endocrinology and Nutrition Service, Hospital Universitario 12 de Octubre, Madrid, Spain.
(8) Department of Endocrinology, Hospital Universitario La Paz, Madrid, Spain.
(9) Department of Endocrinology, Complejo Hospitalario Universitario de Albacete, Albacete, Spain.
(10) Department of Endocrinology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
(11) Department of Endocrinology, Hospital Virgen de la Salud-Complejo Hospitalario de Toledo, Toledo, Spain.
(12) Molecular Diagnostics Units of the Hereditary Cancer Program at the Catalan Institute of Oncology, Barcelona, Spain.
(13) Department of Endocrinology, Clínica Universidad de Navarra, Navarra, Spain.
(14) Department of Pediatrics and Clinical Genetics Unit, Clínica Universidad de Navarra, Navarra, Spain.
(15) Department of Endocrinology, Hospital General Universitario Reina Sofía, Murcia, Spain.
(16) High Risk and Cancer Prevention Group, Medical Oncology Department, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
(17) Department of Endocrinology, Hospital Clínico San Carlos, Madrid, Spain.
(18) Department of Molecular Oncology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
(19) Department of Endocrinology and Nutrition, University Hospital Arnau de Vilanova, IRBLLEIDA, Lleida, Spain, and Department of Pathology, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain.
(20) Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Raras, Madrid, Spain.
(21) 1st Department of Medicine, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany.
(22) Department of Endocrinology, Department of Medical and Surgical Sciences University of Padova, Padova, Italy.
(23) Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland.
(24) Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands.
(25) Department of Pathology, Erasmus University Medical Center, Rotterdam, the Net

Revista: The Journal of Molecular Diagnostics

Fecha: 25-may-2017

Unidad de Genética Clínica Endocrinología y Nutrición

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.

CITA DEL ARTÍCULO  J Mol Diagn. 2017 May 25. pii: S1525-1578(17)30097-1. doi: 10.1016/j.jmoldx.2017.04.009

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