Skip to main content
SpringerLink
Log in

Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

The purpose of the present study is to evaluate the prevalence of the gsp oncogene in Brazilian patients harboring somatotropinomas and non-functioning pituitary adenomas (NFPA). Patients and methods Deoxyribonucleic acid was extracted from 54 somatotropinomas and 14 NFPA. Exons 8 and 9 (including codons 201 and 227, respectively) of the GNAS gene were amplified by polymerase chain reaction (PCR). The PCR products were then purified and sequenced using the same primers. Results The gsp oncogene was found in nine tumors (eight somatotropinomas). The prevalence among somatotropinomas was 15% and among NFPA was 7%. The mutation was found in codon 201 in eight tumors and in codon 227 in one tumor (a somatotropinoma). No differences were found in age, sex, GH, and IGF-I levels or tumor volume at diagnosis between gsp+ and gsp− patients. Conclusion We found a lower than expected prevalence of gsp mutations in somatotropinomas and a similar prevalence in NFPA compared to previous studies from other countries.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Spiegel AM (1996) Mutations in G proteins and G protein-coupled receptors in endocrine disease. J Clin Endocrinol Metab 81:2434–2442. doi:10.1210/jc.81.7.2434

    Article  PubMed  CAS  Google Scholar 

  2. Landis CA, Masters SB, Spada A et al (1989) GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumors. Nature 340:692–696. doi:10.1038/340692a0

    Article  PubMed  CAS  Google Scholar 

  3. Williamson EA, Ince PG, Harrison D et al (1995) G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas. Eur J Clin Invest 25:128–131. doi:10.1111/j.1365-2362.1995.tb01537.x

    Article  PubMed  CAS  Google Scholar 

  4. Riminucci M, Collins MT, Lala R et al (2002) An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma. Mol Pathol 55:58–60. doi:10.1136/mp. 55.1.58

    Article  PubMed  CAS  Google Scholar 

  5. Tordjman K, Stern N, Ouaknine G et al (1993) Activating mutations of the Gs alpha-gene in nonfunctioning pituitary tumors. J Clin Endocrinol Metab 77:765–769. doi:10.1210/jc.77.3.765

    Article  PubMed  CAS  Google Scholar 

  6. Williamson EA, Daniels M, Foster S et al (1994) Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumors. Clin Endocrinol (Oxf) 41:815–820. doi:10.1111/j.1365-2265.1994.tb02798.x

    Article  CAS  Google Scholar 

  7. Landis CA, Harsh G, Lyons J et al (1990) Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. J Clin Endocrinol Metab 71:1416–1420

    PubMed  CAS  Google Scholar 

  8. Drews RT, Gravel RA, Collu R (1992) Identification of G protein alpha subunit mutations in human growth hormone (GH)- and GH/prolactin-secreting pituitary tumors by single-strand conformation polymorphism (SSCP) analysis. Mol Cell Endocrinol 87:125–129. doi:10.1016/0303-7207(92)90240-7

    Article  PubMed  CAS  Google Scholar 

  9. Yoshimoto K, Iwahana H, Fukuda A et al (1993) Rare mutations of the Gs alpha subunit gene in human endocrine tumors. Mutation detection by polymerase chain reaction-primer-introduced restriction analysis. Cancer 72:1386–1393. doi :10.1002/1097-0142(19930815)72:4<1386::AID-CNCR2820720439>3.0.CO;2-J

    Article  PubMed  CAS  Google Scholar 

  10. Hosoi E, Yokogoshi Y, Hosoi E et al (1993) Analysis of the Gs alpha gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues. Acta Endocrinol (Copenh) 129:301–306

    CAS  Google Scholar 

  11. Adams EF, Brockmeier S, Friedmann E et al (1993) Clinical and biochemical characteristics of acromegalic patients harboring gsp-positive and gsp-negative pituitary tumors. Neurosurgery 33:198–203. doi:10.1097/00006123-199308000-00003

    Article  PubMed  CAS  Google Scholar 

  12. Yang I, Park S, Ryu M et al (1996) Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients. Eur J Endocrinol 134:720–726

    Article  PubMed  CAS  Google Scholar 

  13. Shi Y, Tang D, Deng J et al (1998) Detection of gsp oncogene in growth hormone-secreting pituitary adenomas and the study of clinical characteristics of acromegalic patients with gsp-positive pituitary tumors. Chin Med J 111:891–894

    PubMed  CAS  Google Scholar 

  14. Ballaré E, Mantovani S, Lania A et al (1998) Activating mutations of the Gs alpha gene are associated with low levels of Gs alpha protein in growth hormone-secreting tumors. J Clin Endocrinol Metab 83:4386–4390. doi:10.1210/jc.83.12.4386

    Article  PubMed  Google Scholar 

  15. Barlier A, Gunz G, Zamora AJ et al (1998) Prognostic and therapeutic consequences of Gs alpha mutations in somatotroph adenomas. J Clin Endocrinol Metab 83:1604–1610. doi:10.1210/jc.83.5.1604

    Article  PubMed  CAS  Google Scholar 

  16. Buchfelder M, Fahlbusch R, Merz T et al (1999) Clinical correlates in acromegalic patients with pituitary tumors expressing GSP oncogenes. Pituitary 1:181–185. doi:10.1023/A:1009905131334

    Article  PubMed  CAS  Google Scholar 

  17. Johnson MC, Codner E, Eggers M et al (1999) Gps mutations in Chilean patients harboring growth hormone-secreting pituitary tumors. J Pediatr Endocrinol Metab 12:381–387

    PubMed  CAS  Google Scholar 

  18. Kim HJ, Kim MS, Park YJ et al (2001) Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas. J Endocrinol 168:221–226. doi:10.1677/joe.0.1680221

    Article  PubMed  CAS  Google Scholar 

  19. Corbetta S, Ballaré E, Mantovani G et al (2001) Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression. Eur J Clin Invest 31:208–214. doi:10.1046/j.1365-2362.2001.00786.x

    Article  PubMed  CAS  Google Scholar 

  20. Kan B, Esapa C, Sipahi T et al (2003) G protein mutations in pituitary tumors: a study on Turkish patients. Pituitary 6:75–80. doi:10.1023/B:PITU.0000004797.89592.5e

    Article  PubMed  CAS  Google Scholar 

  21. Park C, Yang I, Woo J et al (2004) Somatostatin (SRIF) receptor subtype 2 and 5 gene expression in growth hormone-secreting pituitary adenomas: the relationship with endogenous SRIF activity and response to octreotide. Endocr J 51:227–236. doi:10.1507/endocrj.51.227

    Article  PubMed  CAS  Google Scholar 

  22. Mendoza V, Sosa E, Espinosa-de-Los-Monteros AL et al (2005) GSPalpha mutations in Mexican patients with acromegaly: potential impact on long term prognosis. Growth Horm IGF Res 15:28–32. doi:10.1016/j.ghir.2004.10.001

    Article  PubMed  CAS  Google Scholar 

  23. Yasufuku-Takano J, Takano K, Morita K et al (2006) Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited. Clin Endocrinol (Oxf) 64:91–96. doi:10.1111/j.1365-2265.2005.02423.x

    Article  CAS  Google Scholar 

  24. Metzler M, Luedecke DK, Saeger W et al (2006) Low prevalence of Gs alpha mutations in śomatotroph adenomas of children and adolescents. Cancer Genet Cytogenet 166:146–151. doi:10.1016/j.cancergencyto.2005.11.001

    Article  PubMed  CAS  Google Scholar 

  25. Freda PU, Chung WK, Matsuoka N et al (2007) Analysis of GNAS mutations in 60 growth hormone secreting pituitary tumors: correlation with clinical and pathological characteristics and surgical outcome based on highly sensitive GH and IGF-I criteria for remission. Pituitary 10:275–282. doi:10.1007/s11102-007-0058-2

    Article  PubMed  CAS  Google Scholar 

  26. Spada A, Arosio M, Bochicchio D et al (1990) Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71:1421–1426

    PubMed  CAS  Google Scholar 

  27. Jallad RS, Musolino NR, Salgado LR et al (2005) Treatment of acromegaly with octreotide-LAR: extensive experience in a Brazilian institution. Clin Endocrinol (Oxf) 63:168–175. doi:10.1111/j.1365-2265.2005.02317.x

    Article  CAS  Google Scholar 

  28. Freda PU, Katznelson L, van der Lely AJ et al (2005) Long-acting somatostatin analog therapy of acromegaly: a meta-analysis. J Clin Endocrinol Metab 90:4465–4473. doi:10.1210/jc.2005-0260

    Article  PubMed  CAS  Google Scholar 

  29. Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89:667–674. doi:10.1210/jc.2003-031199

    Article  PubMed  CAS  Google Scholar 

  30. Ayuk J, Clayton RN, Holder G et al (2004) Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab 89:1613–1617. doi:10.1210/jc.2003-031584

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Serviço de Endocrinologia do Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rua Nascimento Silva, 555/101, Ipanema, Rio de Janeiro, Brazil, 22421-020

    Giselle Fernandes Taboada & Mônica Roberto Gadelha

  2. Serviço de Endocrinologia do Hospital Universitário Pedro Ernesto, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil

    Ana Lúcia Osório Tabet

  3. Serviço de Endocrinologia do Hospital Universitário de Brasília, Universidade de Brasília, Brasília, Brazil

    Luciana A. Naves

  4. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Denise Pires de Carvalho

Authors
  1. Giselle Fernandes Taboada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Lúcia Osório Tabet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luciana A. Naves
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Denise Pires de Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mônica Roberto Gadelha
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mônica Roberto Gadelha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taboada, G.F., Tabet, A.L.O., Naves, L.A. et al. Prevalence of gsp oncogene in somatotropinomas and clinically non-functioning pituitary adenomas: our experience. Pituitary 12, 165–169 (2009). https://doi.org/10.1007/s11102-008-0136-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-008-0136-0

Keywords

Search

Navigation