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Genetic stratification of inherited and sporadic phaeochromocytoma and paraganglioma: implications for precision medicine.

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Casey, Ruth 
Neumann, Hartmut PH 
Maher, Eamonn R 


Over the past two decades advances in genomic technologies have transformed knowledge of the genetic basis of phaeochromocytoma and paraganglioma (PPGL). Though traditional teaching suggested that inherited cases accounted for only 10% of all phaeochromocytoma diagnosis, current estimates are at least three times this proportion. Inherited PPGL is a highly genetically heterogeneous disorder but the most frequently results from inactivating variants in genes encoding subunits of succinate dehydrogenase. Expanding knowledge of the genetics of PPGL has been translated into clinical practice by the provision of widespread testing for inherited PPGL. In this review, we explore how the molecular stratification of PPGL is being utilized to enable more personalized strategies for investigation, surveillance and management of affected individuals and their families. Translating recent genetic research advances into clinical service can not only bring benefits through more accurate diagnosis and risk prediction but also challenges when there is a suboptimal evidence base for the clinical consequences or significance of rare genotypes. In such cases, clinical, biochemical, pathological and functional imaging assessments can all contribute to more accurate interpretation and clinical management.



Adrenal Gland Neoplasms, Genetic Testing, Germ-Line Mutation, Humans, Paraganglioma, Pheochromocytoma, Precision Medicine, Signal Transduction, Succinate Dehydrogenase

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Hum Mol Genet

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Oxford University Press (OUP)


All rights reserved
European Research Council (323004)
GIST Support UK (GSUKRC01)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0616-10035)
We apologise to all the authors whose work we were unable to cite because of space constraints. We thank Dr Birke Bausch, University of Freiburg, Germany and Anna Roslyakowa, Department of Surgery, Endocrinology Research Center, Moscow, Russia for their expert input. RC acknowledges support from AMEND and GIST Support UK. ERM acknowledges support from European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre) and Cancer Research UK Cambridge Cancer Centre. The views expressed are those of the authors and not necessarily those of the NHS or NIHR. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve.