title: Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas.
abstract: Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Drive, MC7880, San Antonio, Texas 78229, USA.|Spanish National Cancer Research Centre, CNIO, Calle de Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Toledo
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 20 Rue Leblanc, 75015 Paris, France.|INSERM, UMR970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, 75015, Paris, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Burnichon
authors.affiliation: Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Calle de Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cascon
authors.affiliation: Cancer Genetics Unit, Kolling Institute, Royal North Shore Hospital, St Leonards, University of Sydney, Reserve Road, St Leonards, Sydney, New South Wales 2065, Australia.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Benn
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bayley
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, 58183 Linköping, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Welander
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands.
authors.forename: Carli M
authors.initials: CM
authors.lastname: Tops
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge and NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, CB2 0QQ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Firth
authors.affiliation: Cancer Genetics Unit, Kolling Institute, Royal North Shore Hospital, St Leonards, University of Sydney, Reserve Road, St Leonards, Sydney, New South Wales 2065, Australia.
authors.forename: Trish
authors.initials: T
authors.lastname: Dwight
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy.
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale GB Morgagni 50, 50134, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.affiliation: Familial Cancer Clinic, Veneto Institute of Oncology, IRCCS, Via Gattamelata, 64 Padova, Veneto 35128, Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Opocher
authors.affiliation: Cancer Genetics Unit, Kolling Institute, Royal North Shore Hospital, St Leonards, University of Sydney, Reserve Road, St Leonards, Sydney, New South Wales 2065, Australia.
authors.forename: Roderick
authors.initials: R
authors.lastname: Clifton-Bligh
authors.affiliation: Department of Surgery, Region Östergötland, Linköping University, 581 83 Linköping, Sweden.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge and NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge, CB2 0QQ, UK.
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.affiliation: Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Calle de Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
authors.affiliation: Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 20 Rue Leblanc, 75015 Paris, France.|INSERM, UMR970, Paris Cardiovascular Research Center (PARCC), 56 Rue Leblanc, 75015, Paris, France.
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.affiliation: Division of Hematology and Medical Oncology, Department of Medicine, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Drive, MC7880, San Antonio, Texas 78229, USA.
authors.forename: Patricia L M
authors.initials: PL
authors.lastname: Dahia
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000235:genetics; D003245:Consensus Statements as Topic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods / Q000639:trends*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods / Q000639:trends; D006801:Humans; D010235:Paraganglioma / Q000175:diagnosis* / Q000235:genetics; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000235:genetics