Somatic mutations are frequent events in corticotroph tumor progression causing Nelson's tumor

Perez-Rivas LG, Theodoropoulou M, Puar TH, Fazel J, Stieg MR, Ferrau F, Assie G, Gadelha MR, Deutschbein T, Fragoso MC, Kusters B, Saeger W, Honegger J, Buchfelder M, Korbonits M, Bertherat J, Stalla GK, Hermus AR, Beuschlein F, Reincke M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

European Journal of Endocrinology BioScientifica

Book Volume: 178

Pages Range: 59-65

Journal Issue: 1

DOI: 10.1530/EJE-17-0634

Abstract

Somatic mutations in the ubiquitin-specific protease 8 () gene are frequent in corticotroph tumors causing Cushing's disease (CD). Corticotroph tumor progression, the so-called Nelson's syndrome (NS), is a potentially life-threatening complication of bilateral adrenalectomy in patients with refractory CD that is caused by the development of an ACTH-secreting tumor of the pituitary gland. Whether alterations are also present in progressive Nelson's tumors has not been studied in detail so far.Retrospective, multicenter study involving tumors from 33 patients with progressive corticotroph tumors (29 females) and screening for somatic mutations on the mutational hotspot of the gene in the exon 14 with Sanger sequencing.Fifteen out of 33 tumors (45%) presented with a mutation in the exon 14 of , with c.2159C>A (p.Pro720Gln) being the most frequent (9/33), followed by c.2155_2157delTCC (p.Ser718del, 4/33) and c.2152T>C (p.Ser718Pro, 2/33). This prevalence is similar to that previously reported for CD. Mutations were found exclusively in females. Other variables, such as age at diagnosis with NS, body mass index, hyperpigmentation, visual field defects, adenoma size or mortality, did not significantly differ between patients with wild-type and mutant tumors. Patients with mutant tumors exhibited higher levels of plasma ACTH after surgery (median: 640 vs 112 pg/mL, = 0.03). No differences were observed in ACTH normalization (<50 pg/mL) and tumor control after surgery for Nelson's tumor.Somatic mutations in are common in Nelson's tumors, indicating that they do not drive the corticotroph tumor progression that leads to NS, and may be associated with a less favorable biochemical outcome after surgery for Nelson's tumor.

Authors with CRIS profile

Michael Buchfelder Lehrstuhl für Neurochirurgie

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) University of São Paulo / Universidade de São Paulo (USP) BR Brazil (BR) Radboud University Nijmegen NL Netherlands (NL) Universität Hamburg (UHH) DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Queen Mary University of London GB United Kingdom (GB) Hôpital Cochin FR France (FR) Max-Planck-Institut für Psychiatrie (Deutsche Forschungsanstalt für Psychiatrie) DE Germany (DE) Universidade Federal do Rio de Janeiro (UFRJ) / Federal University of Rio de Janeiro BR Brazil (BR)

How to cite

APA:

Perez-Rivas, L.G., Theodoropoulou, M., Puar, T.H., Fazel, J., Stieg, M.R., Ferrau, F.,... Reincke, M. (2018). Somatic mutations are frequent events in corticotroph tumor progression causing Nelson's tumor. European Journal of Endocrinology, 178(1), 59-65. https://doi.org/10.1530/EJE-17-0634

MLA:

Perez-Rivas, Luis G., et al. "Somatic mutations are frequent events in corticotroph tumor progression causing Nelson's tumor." European Journal of Endocrinology 178.1 (2018): 59-65.

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