Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease

The Journal of Clinical Endocrinology and Metabolism
Fabio R FauczConstantine A Stratakis

Abstract

Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric patients with CD. Clinical, biochemical, and imaging data were compared between patients with and without somatic USP8 mutations. Five different USP8 mutations (three missense, one frameshift, and one in-frame deletion) were identified in 13 patients (31%), all of them located in exon 14 at the previously described mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients with somatic mutations were older at disease presentation [mean 5.1 ± 2.1 standard deviation (SD) vs 13.1 ± 3.6 years, P = 0.03]. Levels of urinary free cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as tumor size and frequency of invasion of the cavernous sinus, were not significantly different between the two groups. How...Continue Reading

References

Dec 6, 2005·Cell·Sebastian M B NijmanRené Bernards
Nov 24, 2006·The Journal of Biological Chemistry·Husam A J Alwan, Jeroen E M van Leeuwen
Apr 7, 2007·Trends in Endocrinology and Metabolism : TEM·Helen L StorrMartin O Savage
May 28, 2009·The Journal of Clinical Endocrinology and Metabolism·Dalia L BatistaConstantine A Stratakis
Jun 6, 2009·Annual Review of Biochemistry·Francisca E Reyes-TurcuKeith D Wilkinson
Mar 13, 2010·The Journal of Pediatrics·Maya B LodishConstantine A Stratakis
Nov 23, 2011·The Journal of Clinical Investigation·Fredric E Wondisford
Nov 23, 2011·The Journal of Clinical Investigation·Hidenori FukuokaShlomo Melmed
Jan 22, 2013·Cellular Signalling·Inez M J MeijerJeroen E M van Leeuwen
Feb 2, 2013·The Journal of Clinical Endocrinology and Metabolism·Russell R LonserEdward H Oldfield
Jun 12, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sanguine ByunZigang Dong
Dec 9, 2014·Nature Genetics·Martin ReinckeMasayuki Komada
Feb 14, 2015·Cell Research·Zeng-Yi MaYao Zhao
Feb 20, 2015·The Journal of Clinical Endocrinology and Metabolism·Paraskevi XekoukiConstantine A Stratakis
May 6, 2015·The Journal of Clinical Endocrinology and Metabolism·Luis G Perez-RivasMartin Reincke
May 26, 2015·Lancet·André LacroixLynnette K Nieman
May 28, 2015·European Journal of Endocrinology·Marily TheodoropoulouMasayuki Komada
Aug 25, 2015·The Journal of Clinical Endocrinology and Metabolism·Ali AfshariConstantine A Stratakis
Sep 9, 2015·Neurosurgery·William F ChandlerDavid E Schteingart
Sep 29, 2015·Trends in Endocrinology and Metabolism : TEM·Silviu SbieraBruno Allolio
Nov 19, 2015·European Journal of Endocrinology·Kyohei HayashiShozo Yamada
Jun 1, 2016·Endocrinology and Metabolism Clinics of North America·Constantine A Stratakis

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Citations

May 24, 2017·Endocrine-related Cancer·Laura C Hernández-RamírezConstantine A Stratakis
Feb 24, 2018·FEBS Letters·Federica CentorrinoChristian Ottmann
Jun 30, 2018·Clinical Endocrinology·Adriana AlbaniMarily Theodoropoulou
Aug 8, 2018·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Adriana AlbaniMarily Theodoropoulou
Jun 22, 2019·Neuro-oncology·Silviu SbieraMartin Fassnacht
Jun 5, 2019·The Journal of Clinical Endocrinology and Metabolism·Michal CohenDov Tiosano
Mar 31, 2018·Journal of the Endocrine Society·Cora BallmannUte I Scholl
Jan 1, 2019·The Journal of Clinical Endocrinology and Metabolism·Christina TatsiMaya B Lodish
Nov 16, 2019·Journal of Clinical Medicine·Hiroshi Nishioka, Shozo Yamada
Apr 2, 2020·The Journal of Clinical Endocrinology and Metabolism·Fanny ChasseloupLaura C Hernández-Ramírez
Jan 9, 2020·Reviews in Endocrine & Metabolic Disorders·Christina Tatsi, Constantine A Stratakis
Jul 10, 2020·JAMA Otolaryngology-- Head & Neck Surgery·Christopher S HongSacit Bulent Omay
Apr 17, 2020·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Vladimir VasilevAlbert Beckers
Mar 24, 2020·Endocrine Reviews·Vinaya Srirangam Nadhamuni, Márta Korbonits
Aug 25, 2020·Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association·Adriana Albani, Marily Theodoropoulou
Aug 30, 2017·Clinical Endocrinology·Adriana AlbaniMartin Reincke
Dec 4, 2019·Expert Review of Endocrinology & Metabolism·Angeline Jia Jia ShenChristopher J Yates
Jul 11, 2018·Endocrine-related Cancer·Catherine GoudieWilliam D Foulkes
Dec 28, 2019·Journal of Clinical Medicine·Christina Tatsi, Constantine A Stratakis
Aug 28, 2018·Frontiers in Endocrinology·Takako Araki, Ning-Ai Liu
Apr 11, 2020·Cancer Management and Research·Xu JingJing Wu
Jul 6, 2019·Pituitary·Ingrid Quevedo WanichiMaria Candida Barisson Villares Fragoso
Nov 5, 2019·Frontiers in Endocrinology·Anna WȩdrychowiczJerzy B Starzyk
Jul 28, 2020·Frontiers in Endocrinology·Idoia Martínez de LaPiscinaConstantine A Stratakis
Nov 23, 2020·The Journal of Clinical Endocrinology and Metabolism·Andrew V UzilovEliza B Geer
Jan 31, 2021·Reviews in Endocrine & Metabolic Disorders·Rosario FerrignoMartin O Savage
Feb 13, 2021·Frontiers in Endocrinology·Mengqi ChangRenzhi Wang
May 18, 2020·Best Practice & Research. Clinical Endocrinology & Metabolism·Christina TatsiConstantine A Stratakis
Feb 26, 2021·The Journal of Clinical Endocrinology and Metabolism·Christina TatsiConstantine A Stratakis
May 15, 2021·Frontiers in Endocrinology·José Miguel Hinojosa-AmayaDaniel Cuevas-Ramos

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