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Genetics of Cushing's disease
Author(s) -
Albani Adriana,
Theodoropoulou Marily,
Reincke Martin
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13457
Subject(s) - cushing's disease , context (archaeology) , biology , mutation , germline mutation , adrenocorticotropic hormone , endocrinology , gene , germline , medicine , somatic cell , genetics , disease , cancer research , hormone , paleontology
Summary Cushing's disease ( CD ) is a rare disabling condition caused by Adrenocorticotropic hormone ( ACTH )‐secreting adenomas of the pituitary. The majority of corticotropic adenomas are monoclonal and occur sporadically. Only rarely does CD arise in the context of genetic familial syndromes. Targeted sequencing of oncogenes and tumour suppressor genes commonly mutated in other tumours did not identify recurrent mutations. In contrast, next generation sequencing allowed us recently to clarify the genetic basis of CD : we identified somatic driver mutations in the ubiquitin‐specific protease 8 ( USP 8) gene in a significant portion of corticotropinomas. These mutations represent a novel and unique mechanism leading to ACTH excess. Inhibition of USP 8 or its downstream signalling pathways could represent a new therapeutic approach for the management of CD . In this review, we will focus on this new evidence and its implication for clinical care of affected patients.