SDHA Immunohistochemistry Detects Germline SDHA Gene Mutations in Apparently Sporadic Paragangliomas and Pheochromocytomas

被引：229

作者：

Korpershoek, Esther ^{[1
]}

Favier, Judith ^{[4
,7
]}

Gaal, Jose ^{[1
]}

Burnichon, Nelly ^{[4
,5
,7
]}

van Gessel, Bram ^{[1
]}

Oudijk, Lindsey ^{[1
]}

Badoual, Cecile ^{[6
,7
]}

Gadessaud, Noemie ^{[4
,7
]}

Venisse, Annabelle ^{[5
]}

Bayley, Jean-Pierre ^{[9
]}

van Dooren, Marieke F. ^{[2
]}

de Herder, Wouter W. ^{[3
]}

Tissier, Frederique ^{[8
,10
]}

Plouin, Pierre-Francois

van Nederveen, Francien H. ^{[1
]}

Dinjens, Winand N. M. ^{[1
]}

Gimenez-Roqueplo, Anne-Paule ^{[4
,5
,7
]}

de Krijger, Ronald R. ^{[1
]}

机构：

[1] Erasmus MC Univ, Med Ctr Rotterdam, Dept Pathol, Josephine Nefkens Inst, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC Univ, Med Ctr Rotterdam, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC Univ, Med Ctr Rotterdam, Dept Endocrinol, NL-3000 CA Rotterdam, Netherlands

[4] Hop Europeen Georges Pompidou, AP HP, INSERM, U970,Paris Cardiovasc Res Ctr PARC, F-75015 Paris, France

[5] Hop Europeen Georges Pompidou, AP HP, Dept Genet, F-75015 Paris, France

[6] Hop Europeen Georges Pompidou, AP HP, Serv Anatomopathol, F-75015 Paris, France

[7] Univ Paris 05, Fac Med, UMR S970, F-75005 Paris, France

[8] Univ Paris 05, CNRS, Inst Cochin, INSERM,UMR 8104,U1016, F-75005 Paris, France

[9] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands

[10] Hop Cochin, AP HP, Serv Anat Pathol, F-75014 Paris, France

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2011年 / 96卷 / 09期

关键词：

CHAIN COMPLEX-II; SUCCINATE-DEHYDROGENASE; FLAVOPROTEIN GENE; LEIGH-SYNDROME; SUBUNIT; PATIENT;

D O I：

10.1210/jc.2011-1043

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context: Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. A recent report described a patient with an abdominal paraganglioma, immunohistochemically negative for SDHA, and identified a causal germline mutation in SDHA. Objective: In this study, we evaluated the significance of SDHA immunohistochemistry in the identification of new patients with SDHA mutations. Setting: This study was performed in the Erasmus Medical Center in Rotterdam (The Netherlands) and the Universite Paris Descartes in Paris (France). Methods: We investigated 316 pheochromocytomas and paragangliomas for SDHA expression. Sequence analysis of SDHA was performed on all tumors that were immunohistochemically negative for SDHA and on a subset of tumors immunohistochemically positive for SDHA. Results: Six tumors were immunohistochemically negative for SDHA. Four tumors from Dutch patients showed a germline c.91C -> T SDHA gene mutation (p.Arg31X). Another tumor (from France) carried a germline SDHA missense mutation c.1753C -> T (p.Arg585Trp). Loss of the wildtype SDHA allele was confirmed by loss of heterozygosity analysis. Sequence analysis of 35 SDHA immunohistochemically positive tumors did not reveal additional SDHA mutations. Conclusions: Our results demonstrate that SDHA immunohistochemistry on paraffin-embedded tumors can reveal the presence of SDHA germline mutations and allowed the identification of SDHA-related tumors in at least 3% of patients affected by apparently sporadic (para) sympathetic paragangliomas and pheochromocytomas. (J Clin Endocrinol Metab 96: E1472-E1476, 2011)

引用

页码：E1472 / E1476

页数：5

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