Toledo, Rodrigo ABurnichon, NellyCascon Soriano, AlbertoBenn, Diana EBayley, Jean-PierreWelander, JennyTops, Carli MFirth, HelenDwight, TrishErcolino, ToninoMannelli, MassimoOpocher, GiuseppeClifton-Bligh, RoderickGimm, OliverMaher, Eamonn RRobledo Batanero, MercedesGimenez-Roqueplo, Anne-PauleDahia, Patricia L M2025-01-172025-01-172017-04Nat Rev Endocrinol . 2017 Apr;13(4):233-247.https://hdl.handle.net/20.500.12105/26057Phaeochromocytomas 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.The authors are grateful to Joakim Krona (Linkoping University, Sweden) for his contributions to this discussion and earlier NGS research in PPGLs; to Peter Soderkvist for his critical involvement in implementing NGS-based studies of PPGLs in Linkoping University, Sweden; and to all colleagues who have advanced our understanding of the genetics of PPGLs through their research. P.L.M.D. is a recipient of awards from the Cancer Prevention and Research Institute of Texas (CPRIT) Individual Investigator Grants RP101202 and RP57154, the Department of Defense CDMRP W81XWH-12-1-0508, the Voelcker Fund and from the National Institutes of Health (NIH)'s National Center for Research Resources and the National Center for Advancing Translational Sciences, through Grant 8UL1TR000149. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. A.-P.G.-R. thanks INSERM and the French National Cancer Institute (INCA) for their financial support to the French registry for SDH-related paraganglioma (PGL.R) and the Groupe des Tumeurs Endocrines, reseau des laboratoires (TENgen) network, respectively. Her research team is supported by Direction Generale de l'Offre de Soins (DGOS), by INCA (INCA-DGOS_8663) and by the European Union's Horizon 2020 research and innovation programme (# 633983). R.A.T. was a recipient of a research fellowship from the Brazilian National Council for Scientific and Technological Development (CNPq). This work was supported in part by a salary grant to N.B. from Cancer Research for PErsonalized Medicine (CARPEM). E.R.M. is a receipt of an ERC Advanced Researcher AwardengVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/RENAL-CELL CARCINOMAGERMLINE MUTATIONSSPORADIC PHEOCHROMOCYTOMASOMATIC MUTATIONSHIF2A MUTATIONSGENE-MUTATIONSSDHX MUTATIONSCOMPLEX-IIACMG RECOMMENDATIONSQUALITY CONTROLAttribution-NonCommercial-NoDerivatives 4.0 International27857127134233-247Nature Review Endocrinologyopen access