Somatic USP8 mutations are frequent events in corticotroph tumor progression causing Nelson's tumor

Imagem de Miniatura
Arquivos
art_PEREZ-RIVAS_Somatic_USP8_mutations_are_frequent_events_in_corticotroph_2018.PDF (327.7 KB)
Citações na Scopus
40
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
BIOSCIENTIFICA LTD
Autores
PEREZ-RIVAS, Luis G.
THEODOROPOULOU, Marily
PUAR, Troy H.
FAZEL, Julia
STIEG, Mareike R.
FERRAU, Francesco
ASSIE, Guillaume
GADELHA, Monica R.
DEUTSCHBEIN, Timo
Citação
EUROPEAN JOURNAL OF ENDOCRINOLOGY, v.178, n.1, p.57-63, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Objective: Somatic mutations in the ubiquitin-specific protease 8 (USP8) 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 USP8 alterations are also present in progressive Nelson's tumors has not been studied in detail so far. Design and Methods: 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 USP8 gene in the exon 14 with Sanger sequencing. Results: Fifteen out of 33 tumors (45%) presented with a mutation in the exon 14 of USP8, 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 USP8 mutant tumors exhibited higher levels of plasma ACTH after surgery (median: 640 vs 112 pg/mL, P = 0.03). No differences were observed in ACTH normalization (<50 pg/mL) and tumor control after surgery for Nelson's tumor. Conclusion: Somatic mutations in USP8 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.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/24944
Referências
  1. Assie G, 2005, PITUITARY, V7, P209
  2. Assie G, 2007, J CLIN ENDOCR METAB, V92, P172, DOI 10.1210/jc.2006-1328
  3. Ayala A, 2014, J NEURO-ONCOL, V119, P235, DOI 10.1007/s11060-014-1508-0
  4. Barber TM, 2010, EUR J ENDOCRINOL, V163, P495, DOI 10.1530/EJE-10-0466
  5. Cazabat L, 2012, J CLIN ENDOCR METAB, V97, pE663, DOI 10.1210/jc.2011-2291
  6. Costenaro F, 2014, CLIN ENDOCRINOL, V80, P411, DOI 10.1111/cen.12300
  7. Daly AF, 2007, J CLIN ENDOCR METAB, V92, P1891, DOI 10.1210/jc.2006-2513
  8. Dimopoulou C, 2014, EUR J ENDOCRINOL, V170, P283, DOI 10.1530/EJE-13-0634
  9. Dinesen PT, 2015, ENDOCRINOL DIABETES, V2015
  10. Georgitsi M, 2007, P NATL ACAD SCI USA, V104, P4101, DOI 10.1073/pnas.0700004104
  11. Graffeo CS, 2017, J NEUROSURG, P1
  12. Hayashi K, 2016, EUR J ENDOCRINOL, V174, P213, DOI 10.1530/EJE-15-0689
  13. Hernandez-Ramirez LC, 2015, J CLIN ENDOCR METAB, V100, pE1242, DOI 10.1210/jc.2015-1869
  14. Igreja S, 2010, HUM MUTAT, V31, P950, DOI 10.1002/humu.21292
  15. Karl M, 1996, J CLIN ENDOCR METAB, V81, P124, DOI 10.1210/jc.81.1.124
  16. Katznelson L, 2013, J CLIN ENDOCR METAB, V98, P1803, DOI 10.1210/jc.2013-1497
  17. Kemink SAG, 1999, J ENDOCRINOL INVEST, V22, P70, DOI 10.1007/BF03345482
  18. Kemink SAG, 2001, CLIN ENDOCRINOL, V54, P45, DOI 10.1046/j.1365-2265.2001.01187.x
  19. Ma ZY, 2015, CELL RES, V25, P306, DOI 10.1038/cr.2015.20
  20. Palermo NE, 2015, CURR OPIN ENDOCRINOL, V22, P313, DOI 10.1097/MED.0000000000000175
  21. Patil CG, 2008, J CLIN ENDOCR METAB, V93, P358, DOI 10.1210/jc.2007-2013
  22. Pereira AM, 2003, J CLIN ENDOCR METAB, V88, P5858, DOI 10.1210/jc.2003-030751
  23. Perez-Rivas LG, 2016, J ENDOCRINOL INVEST, V39, P29, DOI 10.1007/s40618-015-0353-0
  24. Perez-Rivas LG, 2017, ENDOCR-RELAT CANCER, V24, pL73, DOI 10.1530/ERC-17-0054
  25. Perez-Rivas LG, 2015, J CLIN ENDOCR METAB, V100, pE997, DOI 10.1210/jc.2015-1453
  26. Pimentel FR, 2001, J ENDOCRINOL INVEST, V24, P83, DOI 10.1007/BF03343818
  27. Pinto EM, 2011, PITUITARY, V14, P400, DOI 10.1007/s11102-009-0194-y
  28. Preda V, 2014, EUR J ENDOCRINOL, V171, P659, DOI 10.1530/EJE-14-0426
  29. Reincke M, 2015, EUR J ENDOCRINOL, V173, pM23, DOI 10.1530/EJE-15-0265
  30. Reincke M, 2015, NAT GENET, V47, P31, DOI 10.1038/ng.3166
  31. Ritzel K, 2013, J CLIN ENDOCR METAB, V98, P3939, DOI 10.1210/jc.2013-1470
  32. Ronchi CL, 2016, EUR J ENDOCRINOL, V174, P363, DOI 10.1530/EJE-15-1064
  33. Song ZJ, 2016, CELL RES, V10, P1
  34. Sonino N, 1996, J CLIN ENDOCR METAB, V81, P2647, DOI 10.1210/jc.81.7.2647
  35. Stieg M, 2013, EXPT CLIN ENDOCRINOL, V121, P22
  36. Stratakis CA, 2010, CLIN GENET, V78, P457, DOI 10.1111/j.1399-0004.2010.01406.x
  37. Trivellin G, 2016, ENDOCR-RELAT CANCER, V23, P357, DOI 10.1530/ERC-16-0091

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/42
Artigos e Materiais de Revistas Científicas - ODS/03