Cancer Research CR 2010 Workshops
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gimenez-Roqueplo, A.-P.
Right arrow Articles by Jeunemaitre, X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gimenez-Roqueplo, A.-P.
Right arrow Articles by Jeunemaitre, X.
[Cancer Research 63, 5615-5621, September 1, 2003]
© 2003 American Association for Cancer Research

Endocrinology

Mutations in the SDHB Gene Are Associated with Extra-adrenal and/or Malignant Phaeochromocytomas1

Anne-Paule Gimenez-Roqueplo2, Judith Favier, Pierre Rustin, Claudine Rieubland, Malvina Crespin, Valérie Nau, Philippe Khau Van Kien, Pierre Corvol, Pierre-François Plouin and Xavier Jeunemaitre for the COMETE (COrtical and MEdullary Tumour) Network3

AP/HP, Hôpital Européen Georges Pompidou, Département de Génétique Moléculaire [A-P. G-R., C. R., M. C., V. N., P. K. V. K., X. J.]; INSERM U36, Collège de France [A-P. G-R., J. F., P. C., P-F. P., X. J.]; INSERM U393, Hôpital des Enfants Malades [P. R.]; and AP/HP, Hôpital Européen Georges Pompidou, Service d’Hypertension Artérielle [P. C., P-F. P.], Paris

Germ-line mutations in the genes encoding succinate dehydrogenase complex subunits B (SDHB) and D (SDHD) have been reported in familial paragangliomas and apparently sporadic phaeochromocytomas (ASP), but the genotype–phenotype relationships of these mutations are unknown. Eighty-four patients (all but 2 followed up for 8.8 ± 5.7 years) with ASP (57 with adrenal tumors, 27 with extra-adrenal, multiple, malignant, or recurrent tumors) were screened for the major susceptibility genes for phaeochromocytoma (RET, VHL, SDHD, and SDHB). Thirty-three tumors were available for molecular analysis, enzyme assays, and immunohistochemistry. No (0%) RET and 2 (2.4%) VHL mutations were detected. Only two coding single nucleotide polymorphisms in the SDHD gene (G12S and H50R) were found in 6 patients (7%). Conversely, six deleterious mutations in the SDHB gene were identified in 8 patients (9.5%). Ectopic site and recurrence or malignancy were strongly associated with SDHB mutations (7 of 8, 87%, versus 20 of 76, 26%; P = 0.001). Somatic DNA analysis indicated a loss of heterozygosity at chromosome 1p36 (SDHB locus) in 16 of 33 cases (48%). A loss of heterozygosity at the SDHB locus was found in all tumors with SDHB mutation, and assays of respiratory chain enzymes showed a complete loss of complex II catalytic activity. The vascular architecture of tumors with SDHB mutations displayed features typical of malignancy. These data strongly suggest that SDHB gene is a tumor suppressor gene and that the identification of germ-line mutations in SDHB gene in patients with ASPs should be considered as a high-risk factor for malignancy or recurrence.




This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
N. Burnichon, V. Rohmer, L. Amar, P. Herman, S. Leboulleux, V. Darrouzet, P. Niccoli, D. Gaillard, G. Chabrier, F. Chabolle, et al.
The Succinate Dehydrogenase Genetic Testing in a Large Prospective Series of Patients with Paragangliomas
J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 2817 - 2827.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
H. J L M Timmers, A.-P. Gimenez-Roqueplo, M. Mannelli, and K. Pacak
Clinical aspects of SDHx-related pheochromocytoma and paraganglioma
Endocr. Relat. Cancer, June 1, 2009; 16(2): 391 - 400.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Goffrini, T. Ercolino, E. Panizza, V. Giache, L. Cavone, A. Chiarugi, V. Dima, I. Ferrero, and M. Mannelli
Functional study in a yeast model of a novel succinate dehydrogenase subunit B gene germline missense mutation (C191Y) diagnosed in a patient affected by a glomus tumor
Hum. Mol. Genet., May 15, 2009; 18(10): 1860 - 1868.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Mannelli, M. Castellano, F. Schiavi, S. Filetti, M. Giacche, L. Mori, V. Pignataro, G. Bernini, V. Giache, A. Bacca, et al.
Clinically Guided Genetic Screening in a Large Cohort of Italian Patients with Pheochromocytomas and/or Functional or Nonfunctional Paragangliomas
J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1541 - 1547.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
H. K Ghayee, B. Havekes, E. P M Corssmit, G. Eisenhofer, S. R Hammes, Z. Ahmad, A. Tessnow, I. Lazurova, K. T Adams, A. T Fojo, et al.
Mediastinal paragangliomas: association with mutations in the succinate dehydrogenase genes and aggressive behavior
Endocr. Relat. Cancer, March 1, 2009; 16(1): 291 - 299.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Peczkowska, Z. Erlic, M. M. Hoffmann, M. Furmanek, J. Cwikla, A. Kubaszek, A. Prejbisz, Z. Szutkowski, A. Kawecki, K. Chojnowski, et al.
Impact of Screening Kindreds for SDHD p.Cys11X as a Common Mutation Associated with Paraganglioma Syndrome Type 1
J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4818 - 4825.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. T. Adler, G. Y. Meyer-Rochow, H. Chen, D. E. Benn, B. G. Robinson, R. S. Sippel, and S. B. Sidhu
Pheochromocytoma: Current Approaches and Future Directions
Oncologist, July 1, 2008; 13(7): 779 - 793.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A Cascon, I Landa, E Lopez-Jimenez, A Diez-Hernandez, M Buchta, C Montero-Conde, S Leskela, L J Leandro-Garcia, R Leton, C Rodriguez-Antona, et al.
Molecular characterisation of a common SDHB deletion in paraganglioma patients
J. Med. Genet., April 1, 2008; 45(4): 233 - 238.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Lima, T. Feijao, A. Ferreira da Silva, I. Pereira-Castro, G. Fernandez-Ballester, V. Maximo, A. Herrero, L. Serrano, M. Sobrinho-Simoes, and G. Garcia-Rostan
High Frequency of Germline Succinate Dehydrogenase Mutations in Sporadic Cervical Paragangliomas in Northern Spain: Mitochondrial Succinate Dehydrogenase Structure-Function Relationships and Clinical-Pathological Correlations
J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4853 - 4864.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Amar, E. Baudin, N. Burnichon, S. Peyrard, S. Silvera, J. Bertherat, X. Bertagna, M. Schlumberger, X. Jeunemaitre, A.-P. Gimenez-Roqueplo, et al.
Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas
J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3822 - 3828.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
F. H. van Nederveen, E. Korpershoek, J. W.M. Lenders, R. R. de Krijger, and W. N.M. Dinjens
Somatic SDHB Mutation in an Extraadrenal Pheochromocytoma
N. Engl. J. Med., July 19, 2007; 357(3): 306 - 308.
[Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
E. Korpershoek, B.-J. Petri, F. H van Nederveen, W. N M Dinjens, A. A Verhofstad, W. W de Herder, S. Schmid, A. Perren, P. Komminoth, and R. R de Krijger
Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma
Endocr. Relat. Cancer, June 1, 2007; 14(2): 453 - 462.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Scholz, G. Eisenhofer, K. Pacak, H. Dralle, and H. Lehnert
Current Treatment of Malignant Pheochromocytoma
J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1217 - 1225.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. J. L. M. Timmers, A. Kozupa, G. Eisenhofer, M. Raygada, K. T. Adams, D. Solis, J. W. M. Lenders, and K. Pacak
Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients with Succinate Dehydrogenase Subunit B-Associated Pheochromocytomas and Paragangliomas
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 779 - 786.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. M. Brouwers, G. Eisenhofer, J. J. Tao, J. A. Kant, K. T. Adams, W. M. Linehan, and K. Pacak
High Frequency of SDHB Germline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4505 - 4509.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. J. Pollard, M. El-Bahrawy, R. Poulsom, G. Elia, P. Killick, G. Kelly, T. Hunt, R. Jeffery, P. Seedhar, J. Barwell, et al.
Expression of HIF-1{alpha}, HIF-2{alpha} (EPAS1), and Their Target Genes in Paraganglioma and Pheochromocytoma with VHL and SDH Mutations
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4593 - 4598.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
T. H. Pham, C. Moir, G. B. Thompson, A. E. Zarroug, C. E. Hamner, D. Farley, J. van Heerden, A. N. Lteif, and W. F. Young Jr
Pheochromocytoma and Paraganglioma in Children: A Review of Medical and Surgical Management at a Tertiary Care Center
Pediatrics, September 1, 2006; 118(3): 1109 - 1117.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
B. G. Slane, N. Aykin-Burns, B. J. Smith, A. L. Kalen, P. C. Goswami, F. E. Domann, and D. R. Spitz
Mutation of Succinate Dehydrogenase Subunit C Results in Increased O2{middle dot}-, Oxidative Stress, and Genomic Instability.
Cancer Res., August 1, 2006; 66(15): 7615 - 7620.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. Jimenez, G. Cote, A. Arnold, and R. F. Gagel
Should Patients with Apparently Sporadic Pheochromocytomas or Paragangliomas be Screened for Hereditary Syndromes?
J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2851 - 2858.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
E. R Woodward and E. R Maher
Von Hippel-Lindau disease and endocrine tumour susceptibility.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 415 - 425.
[Abstract] [Full Text] [PDF]

Home page
 Br Med BullHome page
E. R. Maher
Genetics of phaeochromocytoma
Br. Med. Bull., June 1, 2006; 79-80(1): 141 - 151.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
W. F. Young Jr and A. L. Abboud
Paraganglioma--all in the family.
J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 790 - 792.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. E. Benn, A.-P. Gimenez-Roqueplo, J. R. Reilly, J. Bertherat, J. Burgess, K. Byth, M. Croxson, P. L. M. Dahia, M. Elston, O. Gimm, et al.
Clinical Presentation and Penetrance of Pheochromocytoma/Paraganglioma Syndromes
J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 827 - 836.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. Amar, J. Bertherat, E. Baudin, C. Ajzenberg, B. Bressac-de Paillerets, O. Chabre, B. Chamontin, B. Delemer, S. Giraud, A. Murat, et al.
Genetic Testing in Pheochromocytoma or Functional Paraganglioma
J. Clin. Oncol., December 1, 2005; 23(34): 8812 - 8818.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P.J. Pollard, J.J. Briere, N.A. Alam, J. Barwell, E. Barclay, N.C. Wortham, T. Hunt, M. Mitchell, S. Olpin, S.J. Moat, et al.
Accumulation of Krebs cycle intermediates and over-expression of HIF1{alpha} in tumours which result from germline FH and SDH mutations
Hum. Mol. Genet., August 1, 2005; 14(15): 2231 - 2239.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
L Simi, R Sestini, P Ferruzzi, M S Gagliano, F Gensini, M Mascalchi, L Guerrini, C Pratesi, P Pinzani, G Nesi, et al.
Phenotype variability of neural crest derived tumours in six Italian families segregating the same founder SDHD mutation Q109X
J. Med. Genet., August 1, 2005; 42(8): e52 - e52.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Cascon, A. Cebrian, M. Pollan, S. Ruiz-Llorente, C. Montero-Conde, R. Leton, R. Gutierrez, F. Lesueur, R. L. Milne, O. Gonzalez-Albarran, et al.
Succinate Dehydrogenase D Variants Do Not Constitute a Risk Factor for Developing C Cell Hyperplasia or Sporadic Medullary Thyroid Carcinoma
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2127 - 2130.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Eisenhofer, D. S. Goldstein, P. Sullivan, G. Csako, F. M. Brouwers, E. W. Lai, K. T. Adams, and K. Pacak
Biochemical and Clinical Manifestations of Dopamine-Producing Paragangliomas: Utility of Plasma Methoxytyramine
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2068 - 2075.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Amar, A. Servais, A.-P. Gimenez-Roqueplo, F. Zinzindohoue, G. Chatellier, and P.-F. Plouin
Year of Diagnosis, Features at Presentation, and Risk of Recurrence in Patients with Pheochromocytoma or Secreting Paraganglioma
J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2110 - 2116.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
G. Eisenhofer, S. R Bornstein, F. M Brouwers, N.-K. V Cheung, P. L Dahia, R. R de Krijger, T. J Giordano, L. A Greene, D. S Goldstein, H. Lehnert, et al.
Malignant pheochromocytoma: current status and initiatives for future progress
Endocr. Relat. Cancer, September 1, 2004; 11(3): 423 - 436.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
B E Baysal, J E Willett-Brozick, P A A Filho, E C Lawrence, E N Myers, and R E Ferrell
An Alu-mediated partial SDHC deletion causes familial and sporadic paraganglioma
J. Med. Genet., September 1, 2004; 41(9): 703 - 709.
[Full Text] [PDF]

Home page
 JAMAHome page
H. P. H. Neumann, C. Pawlu, M. Peczkowska, B. Bausch, S. R. McWhinney, M. Muresan, M. Buchta, G. Franke, J. Klisch, T. A. Bley, et al.
Distinct Clinical Features of Paraganglioma Syndromes Associated With SDHB and SDHD Gene Mutations
JAMA, August 25, 2004; 292(8): 943 - 951.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.