The Proteome of Bilateral Macronodular Adrenocortical Disease (BMAD) Shows Different Profiles Correlating with the Genetic Causes and Reveals Specific Dysregulation of RNA Polymerase II and Cholesterol Biosynthesis Enzymes

Bouys L, Chiodini I, Arlt W, Reincke M, Bertherat J (2021) Update on primary bilateral macronodular adrenal hyperplasia (PBMAH). Endocrine 71:595–603. https://doi.org/10.1007/s12020-021-02645-w

Article  PubMed  CAS  Google Scholar 

Cavalcante IP, Berthon A, Fragoso MC, Reincke M, Stratakis CA, Ragazzon B, Bertherat J (2022) Primary bilateral macronodular adrenal hyperplasia: definitely a genetic disease. Nat Rev Endocrinol 18:699–711. https://doi.org/10.1038/s41574-022-00718-y

Article  PubMed  CAS  Google Scholar 

Mete O, Erickson LA, Juhlin CC, Krijger RR, Sasano H, Volante M, Papotti MG (2022) Overview of the 2022 WHO Classification of Adrenal Cortical Tumors. Endocr Pathol 33:155–196. https://doi.org/10.1007/s12022-022-09710-8

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bertherat J, Bourdeau I, Bouys L, Chasseloup F, Kamenický P, Lacroix A (2023) Clinical, Pathophysiologic, Genetic, and Therapeutic Progress in Primary Bilateral Macronodular Adrenal Hyperplasia. Endocrine Reviews 44:567–628. https://doi.org/10.1210/endrev/bnac034

Article  PubMed  Google Scholar 

Violon F, Bouys L, Berthon A, Ragazzon B, Barat M, Perlemoine K, Guignat L, Terris B, Bertherat J, Sibony M (2023) Impact of Morphology in the Genotype and Phenotype Correlation of Bilateral Macronodular Adrenocortical Disease (BMAD): A Series of Clinicopathologically Well-Characterized 35 Cases. Endocr Pathol 34:179–199. https://doi.org/10.1007/s12022-023-09751-7

Article  PubMed  CAS  Google Scholar 

Chasseloup F, Bourdeau I, Tabarin A, et al (2021) Loss of KDM1A in GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing’s syndrome: a multicentre, retrospective, cohort study. The Lancet Diabetes & Endocrinology 9:813–824. https://doi.org/10.1016/S2213-8587(21)00236-9

Article  CAS  Google Scholar 

Vaczlavik A, Bouys L, Violon F, et al (2022) KDM1A inactivation causes hereditary food-dependent Cushing syndrome. Genetics in Medicine 24:374–383. https://doi.org/10.1016/j.gim.2021

Article  PubMed  CAS  Google Scholar 

Violon F, Bouys L, Vaduva P, Chansavang A, Vaquier L, Letourneur F, Izac B, Giannone G, De Murat D, Gaillard M, Berthon A, Ragazzon B, Pasmant E, Sibony M, Bertherat J (2024) Somatic Molecular Heterogeneity in Bilateral Macronodular Adrenocortical Disease (BMAD) Differs Among the Pathological Subgroups. Endocr Pathol 35:194–206. https://doi.org/10.1007/s12022-024-09824-1

Article  PubMed  CAS  Google Scholar 

Correa R, Zilbermint M, Berthon A, Espiard S, Batsis M, Papadakis G, Xebouki P, Lodish M, Bertherat J, Faucz F, Stratakis C (2015) The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia. European Journal of Endocrinology 173:435–440. https://doi.org/10.1530/EJE-15-0205

Article  PubMed  PubMed Central  CAS  Google Scholar 

Jin P, Janjua MU, Zhang Q, Dong C, Yang Y, Mo Z (2018) Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal hyperplasia that started with exophthalmos: a case report. J Med Case Reports 12:13. https://doi.org/10.1186/s13256-017-1529-3

Article  Google Scholar 

Bouys L, Vaduva P, Jouinot A, et al (2025) KDM1A genetic alterations, a rare cause of primary bilateral macronodular adrenal hyperplasia, strongly associated with food-dependent Cushing’s syndrome: results of its systematic germline screening in 301 index cases and genotype/phenotype correlation. European Journal of Endocrinology 192:119–127. https://doi.org/10.1093/ejendo/lvaf016

Article  PubMed  CAS  Google Scholar 

Assié G, Libé R, Espiard S, et al (2013) ARMC5 Mutations in Macronodular Adrenal Hyperplasia with Cushing’s Syndrome. The New England Journal of Medicine 10. https://doi.org/10.1056/NEJMoa1304603

Sasano H, Suzuki T, Nagura H (1994) ACTH-independent macronodular adrenocortical hyperplasia: immunohistochemical and in situ hybridization studies of steroidogenic enzymes. Mod Pathol 7:215–219.

PubMed  CAS  Google Scholar 

De Arruda Botelho MLA, Nishi MY, Ribeiro KB, Zerbini MCN (2023) Morphological Harbingers of ARMC5-Pathogenic Variant-Related Bilateral Macronodular Adrenocortical Disease. Endocr Pathol 34:200–212. https://doi.org/10.1007/s12022-023-09761-5

Article  PubMed  CAS  Google Scholar 

Swierczynska MM, Betz MJ, Colombi M, Dazert E, Jenö P, Moes S, Pfaff C, Glatz K, Reincke M, Beuschlein F, Donath MY, Hall MN (2019) Proteomic Landscape of Aldosterone-Producing Adenoma. Hypertension 73:469–480. https://doi.org/10.1161/HYPERTENSIONAHA.118.11733

Article  PubMed  CAS  Google Scholar 

Sohier P, Sanson R, Leduc M, Audebourg A, Broussard C, Salnot V, Just PA, Pasmant E, Mayeux P, Guillonneau F, Romagnolo B, Perret C, Terris B (2020) Proteome analysis of formalin-fixed paraffin‐embedded colorectal adenomas reveals the heterogeneous nature of traditional serrated adenomas compared to other colorectal adenomas. The Journal of Pathology 250:251–261. https://doi.org/10.1002/path.5366

Article  PubMed  CAS  Google Scholar 

Demichev V, Messner CB, Vernardis SI, Lilley KS, Ralser M (2020) DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput. Nat Methods 17:41–44. https://doi.org/10.1038/s41592-019-0638-x

Article  PubMed  CAS  Google Scholar 

Asleh K, Negri GL, Spencer Miko SE, Colborne S, Hughes CS, Wang XQ, Gao D, Gilks B, Chia S, Nielsen TO, Morin GB (2022) Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes. Nat Commun 13:896. https://doi.org/10.1038/s41467-022-28524-0

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lao L, Bourdeau I, Gagliardi L, He X, Shi W, Hao B, Tan M, Hu Y, Peng J, Coulombe B, Torpy DJ, Scott HS, Lacroix A, Luo H, Wu J (2022) ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia. Nucleic Acids Research 50:6343–6367. https://doi.org/10.1093/nar/gkac483

Article  PubMed  PubMed Central  CAS  Google Scholar 

Luo H, Lao L, Au KS, Northrup H, He X, Forget D, Gauthier MS, Coulombe B, Bourdeau I, Shi W, Gagliardi L, Fragoso M, Peng J, Wu J (2024) ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans. Genome Biol 25:19. https://doi.org/10.1186/s13059-023-03147-w

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dürr UHN, Waskell L, Ramamoorthy A (2007) The cytochromes P450 and b5 and their reductases—Promising targets for structural studies by advanced solid-state NMR spectroscopy. Biochimica et Biophysica Acta (BBA) - Biomembranes 1768:3235–3259. https://doi.org/10.1016/j.bbamem.2007.08.007

Article  PubMed  CAS  Google Scholar 

Storbeck K-H, Swart AC, Fox CL, Swart P (2015) Cytochrome b5 modulates multiple reactions in steroidogenesis by diverse mechanisms. The Journal of Steroid Biochemistry and Molecular Biology 151:66–73. https://doi.org/10.1016/j.jsbmb.2014.11.024

Article  PubMed  CAS  Google Scholar 

Bhatt MR, Khatri Y, Rodgers RJ, Martin LL (2017) Role of cytochrome b5 in the modulation of the enzymatic activities of cytochrome P450 17α-hydroxylase/17,20-lyase (P450 17A1). The Journal of Steroid Biochemistry and Molecular Biology 170:2–18. https://doi.org/10.1016/j.jsbmb.2016.02.033

Article  PubMed  CAS  Google Scholar 

Okuno Y, Fukuhara A, Otsuki M, Shimomura I (2022) ARMC5-CUL3 E3 ligase targets full-length SREBF in adrenocortical tumors. JCI Insight 7:e151390. https://doi.org/10.1172/jci.insight.151390

Article  PubMed  PubMed Central  Google Scholar 

Uota A, Okuno Y, Fukuhara A, Sasaki S, Kobayashi S, Shimomura I (2024) ARMC5 selectively degrades SCAP-free SREBF1 and is essential for fatty acid desaturation in adipocytes. Journal of Biological Chemistry 300:107953. https://doi.org/10.1016/j.jbc.2024.107953

Article  PubMed  PubMed Central  CAS  Google Scholar 

Espiard S, Drougat L, Libé R, et al (2015) ARMC5 Mutations in a Large Cohort of Primary Macronodular Adrenal Hyperplasia: Clinical and Functional Consequences. The Journal of Clinical Endocrinology & Metabolism 100:E926–E935. https://doi.org/10.1210/jc.2014-4204

Article  Google Scholar 

Cavalcante IP, Nishi M, Zerbini MCN, et al (2018) The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH). Molecular and Cellular Endocrinology 460:36–46. https://doi.org/10.1210/jc.2014-4204

Article  PubMed  Google Scholar 

Comments (0)

No login
gif