Abstract
Allelic loss of the long arm of chromosome 11 is frequent in neuroendocrine tumors (NET) of different organs. However, the MEN1 gene on 11q13 is mutated only in a subset of NET and allelic losses on 11q frequently extend to the telomere. In this genetic region lies the tumor suppressor gene SDHD which is associated with hereditary paragangliomas (PGL1). We sought to determine whether SDHD plays a role in the development of sporadic NET. By mutation and deletion analysis of SDHD we were unable to detect any SDHD mutation in 45 NET of the lung, gastrointestinal tract, pancreas or parathyroid. However, we found allelic deletions in 20 to 50% of all tumors but parathyroid adenomas. Furthermore, we found heterozygous germline variants in 2/8 paragangliomas. A first case of variant c.149 A>G (H50R) was found in a patient with an extra-adrenal pheochromocytoma, the other variant c.34 G>A (G12S) in a patient with a paratracheal paraganglioma, C-cell hyperplasia of the thyroid and hyperplasia of ACTH-producing cells of the pituitary gland. Both variants were absent in 93 controls. Our results demonstrate that somatic SDHD mutations are rare in sporadic NET. However, LOH alone could lead to a complete loss of function since SDHD is an imprinted gene. Furthermore, we describe two germline variants possibly causing hereditary paragangliomas.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Badenhop RF, Cherian S, Lord RS, Baysal BE, Taschner PE, Schofield PR . 2001 Genes Chromosomes Cancer 31: 255–263
Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard III CW, Cornelisse CJ, Devilee P, Devlin B . 2000 Science 287: 848–851
Baysal BE, van Schothorst EM, Farr JE, Grashof P, Myssiorek D, Rubinstein WS, Taschner P, Cornelisse CJ, Devlin B, Devilee P, Richard 3rd CW . 1999 Hum. Genet. 104: 219–225
Chakrabarti R, Srivatsan ES, Wood TF, Eubanks PJ, Ebrahimi SA, Gatti RA, Passaro EJ, Sawicki MP . 1998 Genes Chromosomes Cancer 22: 130–137
D'Adda T, Keller G, Bordi C, Hofler H . 1999 Lab. Invest. 79: 671–677
Dannenberg H, Speel EJ, Zhao J, Saremaslani P, van Der Harst E, Roth J, Heitz PU, Bonjer HJ, Dinjens WN, Mooi WJ, Komminoth P, de Krijger RR . 2000 Am. J. Pathol. 157: 353–359
Eubanks PJ, Sawicki MP, Samara GJ, Gatti R, Nakamura Y, Tsao D, Johnson C, Hurwitz M, Wan Y-JY, Passaro E . 1994 Am. J. Surg. 167: 180–185
Farnebo F, Kytola S, Teh BT, Dwight T, Wong FK, Hoog A, Elvius M, Wassif WS, Thompson NW, Farnebo LO, Sandelin K, Larsson C . 1999 J. Clin. Endocrinol. Metab. 84: 3775–3780
Farnebo F, Teh BT, Dotzenrath C, Wassif WS, Svensson A, White I, Betz R, Goretzki P, Sandelin K, Farnebo LO, Larsson C . 1997 Hum. Genet. 99: 342–349
Friedman E, De Marco L, Gejman PV, Norton JA, Bale AE, Aurbach GD, Spiegel AM, Marx SJ . 1992 Cancer Res. 52: 6804–6809
Gimm O, Armanios M, Dziema H, Neumann HP, Eng C . 2000 Cancer Res. 60: 6822–6825
Gortz B, Roth J, Krahenmann A, de Krijger RR, Muletta-Feurer S, Rutimann K, Saremaslani P, Speel EJ, Heitz PU, Komminoth P . 1999 Am. J. Pathol. 154: 429–436
Hagerhall C . 1997 Biochim. Biophys. Acta. 1320: 107–141
Hirawake H, Taniwaki M, Tamura A, Amino H, Tomitsuka E, Kita K . 1999 Biochim. Biophys Acta 1412: 295–300
Iwasaki H . 1996 Int. Surg. 81: 71–76
Jakobovitz G, Nass D, Demarco L, Barbosa A, Simoni FB, Rechavi G, Friedman E . 1996 J. Clin. Endocrinol. Metab. 81: 3164–3167
Koehler CM . 2000 FEBS Lett. 476: 27–31
Komminoth P, Kunz E, Hiort O, Schroder S, Matias-Guiu X, Christiansen G, Roth J, Heitz PU . 1994 Am. J. Pathol. 145: 922–929
Malik K, Salpekar A, Hancock A, Moorwood K, Jackson S, Charles A, Brown KW . 2000 Cancer Res. 60: 2356–2360
Perren A, Roth J, Muletta-Feurer S, Saremaslani P, Speel EJ, Heitz PU, Komminoth P . 1998 J. Pathol. 186: 363–371
Petzmann S, Ullmann R, Klemen H, Renner H, Popper HH . 2001 Hum. Pathol. 32: 333–338
Pfanner N . 2000 Curr. Biol. 10: R412–R415
Rigaud G, Missiaglia E, Moore PS, Zamboni G, Falconi M, Talamini G, Pesci A, Baron A, Lissandrini D, Rindi G, Grigolato P, Pederzoli P, Scarpa A . 2001 Cancer Res. 61: 285–292
Scheffler IE . 1998 Prog. Nucleic Acids. Res. Mol. Biol. 60: 267–315
Speel EJ, Richter J, Moch H, Egenter C, Saremaslani P, Rutimann K, Zhao J, Barghorn A, Roth J, Heitz PU, Komminoth P . 1999 Am. J. Pathol. 155: 1787–1794
van der Mey AG, Maaswinkel-Mooy PD, Cornelisse CJ, Schmidt PH, van de Kamp JJ . 1989 Lancet 2: 1291–1294
Walch AK, Zitzelsberger HF, Aubele MM, Mattis AE, Bauchinger M, Candidus S, Prauer HW, Werner M, Hofler H . 1998 Am. J. Pathol. 153: 1089–1098
Zhao J, de Krijger RR, Meier D, Speel EJ, Saremaslani P, Muletta-Feurer S, Matter C, Roth J, Heitz PU, Komminoth P . 2000 Am. J. Pathol. 157: 1431–1438
Acknowledgements
Supported by Swiss Cancer League grant SKL-997-02-2000 and Swiss National Science Foundation grant 31-618845.00.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Perren, A., Barghorn, A., Schmid, S. et al. Absence of somatic SDHD mutations in sporadic neuroendocrine tumors and detection of two germline variants in paraganglioma patients. Oncogene 21, 7605–7608 (2002). https://doi.org/10.1038/sj.onc.1205812
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205812
Keywords
This article is cited by
-
Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients
Hereditary Cancer in Clinical Practice (2016)
-
Molecular profiles of gastroenteropancreatic endocrine tumors
Virchows Archiv (2007)
-
LOH on chromosome 11q, but not SDHD and men1 mutations was frequently detectable in chinese patients with pheochromocytoma and paraganglioma
Endocrine (2006)