title: Rethinking pheochromocytomas and paragangliomas from a genomic perspective.
abstract: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors of neural crest origin. These tumors are caused by germline or somatic mutations in known susceptibility genes in up to 70% of cases. Over the past few years, the emergence of high-throughput technologies has enabled the unprecedented characterization of genomic alterations in PCC/PGL, and has improved our understanding of the molecular mechanisms that distinguish the different tumor subtypes. Integrated genomic analyses have shown that the mutation status of PCC/PGL susceptibility genes strongly correlates with multi-omics data. These observations not only emphasize the role of the long-standing susceptibility genes as the main drivers of PCC/PGL tumorigenesis, but also illustrate the functional interdependence between genomic and epigenomic alterations. In this review, we discuss the genomic landscape underlying PCC/PGL, its functional consequences for tumorigenesis and tumor progression, and the potential clinical relevance of this knowledge for the application of precision medicine for patients with PCC/PGL.
authors.affiliation: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: L J
authors.initials: LJ
authors.lastname: Castro-Vega
authors.affiliation: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Lepoutre-Lussey
authors.affiliation: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Department of Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors.forename: A-P
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.affiliation: INSERM, UMR970, Paris-Cardiovascular Research Center, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-8190-5853
authors.initials: J
authors.lastname: Favier
mesh_terms: D059472:Exome; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D009154:Mutation; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology; D010235:Paraganglioma / Q000235:genetics* / Q000473:pathology; D010673:Pheochromocytoma / Q000235:genetics* / Q000473:pathology