Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas
Year: 2016
Type: review
Abstract: As a large number of genes have been implicated in the development of hereditary phaeochromocytomas and paragangliomas (PPGLs), next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening. This Consensus Statement proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. 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.
Source: Nature Reviews Endocrinology
Authors: The NGS in PPGL (NGSnPPGL) Study Group, Rodrigo A. Toledo, Nelly Burnichon, Alberto Cascon, Diana E. Benn, Jean-Pierre Bayley, Jenny Welander, Carli M. Tops, Helen Firth, Trish Dwight, Tonino Ercolino, Massimo Mannelli, Giuseppe Opocher, Roderick Clifton-Bligh, Oliver Gimm, Eamonn R. Maher, Mercedes Robledo, Anne-Paule Gimenez-Roqueplo, Patricia L. M. Dahia
Institutions: The University of Texas at San Antonio Health Science Center, Spanish National Cancer Research Centre, Sorbonne Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Université Paris Descartes, Inserm, Instituto de Salud Carlos III, Centre for Biomedical Network Research on Rare Diseases, Paris Cardiovascular Research Center, The University of Sydney, Royal North Shore Hospital, Leiden University Medical Center, Linköping University, University of Cambridge, NIHR Cambridge Biomedical Research Centre, University of Florence, Istituto Oncologico Veneto, Region Östergötland
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: U.S. Department of Defense, Cancer Prevention and Research Institute of Texas, Max and Minnie Tomerlin Voelcker Fund, European Commission, Institut National de la Santé et de la Recherche Médicale, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Linköpings Universitet, Institut National Du Cancer, Direction Générale de l’offre de Soins, National Institutes of Health, National Cancer Institute, National Center for Research Resources, National Center for Advancing Translational Sciences, Congressionally Directed Medical Research Programs
Awards: G1376570166, COMETE network, towards an easy-to use adrenal cancer/tumour identity card (COMETE-TACTIC), Genetic and Molecular Investigation of Pheochromocytoma Susceptibility and Autophagy, G2217690358, GENETIC AND MOLECULAR INVESTIGATION OF PHEOCHROMOCYTOMA SUSCEPTIBILITY AND AUTOPHAGY, G4119534169, G434337789, G5324093878, G5351884628, Institute for Integration of Medicine & Science: A Partnership to Improve Health, G5850682332, Application of omics-based strategies for improved diagnosis and treatment of endocrine hypertension, G9000238961
OpenAlex ID: W2556416067