BMC Medical Genetics | |
Paraganglioma and pheochromocytoma upon maternal transmission of SDHD mutations | |
Frederik J Hes4  Jeroen C Jansen1  Peter Devilee8  Ronald R de Krijger3  Winand NM Dinjens3  Eleonora PM Corssmit5  Barbara McGillivray6  Esther Korpershoek3  Conny A van der Meer2  Attje S Hoekstra7  Jennifer Nuk6  Rogier A Oldenburg2  Jean-Pierre Bayley7  | |
[1] Department of Otorhinolaryngology, Leiden University Medical Center, Leiden, the Netherlands;Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands;Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands;Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands;Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands;Hereditary Cancer Program, BC Cancer Agency, Vancouver, Canada;Department of Human Genetics, Leiden University Medical Center, PZ S-04, Leiden, 2300, RC, the Netherlands;Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands | |
关键词: Parent-of-origin; Imprinting; SDHD; Pheochromocytoma; Paraganglioma; | |
Others : 1090456 DOI : 10.1186/s12881-014-0111-8 |
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received in 2014-01-14, accepted in 2014-09-24, 发布年份 2014 | |
【 摘 要 】
Background
The SDHD gene encodes a subunit of the mitochondrial tricarboxylic acid cycle enzyme and tumor suppressor, succinate dehydrogenase. Mutations in this gene show a remarkable pattern of parent-of-origin related tumorigenesis, with almost all SDHD-related cases of head and neck paragangliomas and pheochromocytomas attributable to paternally-transmitted mutations.
Methods
Here we explore the underlying molecular basis of three cases of paraganglioma or pheochromocytoma that came to our attention due to apparent maternal transmission of an SDHD mutation. We used DNA analysis of family members to establish the mode of inheritance of each mutation. Genetic and immunohistochemical studies of available tumors were then carried out to confirm SDHD-related tumorigenesis.
Results
We found convincing genetic and immunohistochemical evidence for the maternally-related occurrence of a case of pheochromocytoma, and suggestive evidence in a case of jugular paraganglioma. The third case appears to be a phenocopy, a sporadic paraganglioma in an SDHD mutation carrier with no immunohistochemical or DNA evidence to support a causal link between the mutation and the tumor. Microsatellite analysis in the tumor of patient 1 provided evidence for somatic recombination and loss of the paternal region of chromosome 11 including SDHD and the maternal chromosome including the centromere and the p arm.
Conclusions
Transmission of SDHD mutations via the maternal line can, in rare cases, result in tumorigenesis. Despite this finding, the overwhelming majority of carriers of maternally-transmitted mutations will remain tumor-free throughout life.
【 授权许可】
2014 Bayley et al.; licensee BioMed Central Ltd.
【 预 览 】
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20150128161043952.pdf | 1538KB | download | |
Figure 4. | 125KB | Image | download |
Figure 3. | 161KB | Image | download |
Figure 2. | 88KB | Image | download |
Figure 1. | 161KB | Image | download |
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【 参考文献 】
- [1]Lack E: Atlas of Tumor Pathology: Tumors of the Adrenal Gland and Extra-Adrenal Paraganglia. In AFIP Fasicle No. 19. American Registry of Pathology, Washington DC; 1997.
- [2]Jansen JC, van den BR, Kuiper A, Van Der Mey AG, Zwinderman AH, Cornelisse CJ: Estimation of growth rate in patients with head and neck paragangliomas influences the treatment proposal. Cancer 2000, 88(12):2811-2816.
- [3]Petri BJ, van Eijck CH, de Herder WW, Wagner A, de Krijger RR: Phaeochromocytomas and sympathetic paragangliomas. Br J Surg 2009, 96(12):1381-1392.
- [4]Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, vdM A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B: Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000, 287(5454):848-851.
- [5]Astuti D, Latif F, Dallol A, Dahia PL, Douglas F, George E, Skoldberg F, Husebye ES, Eng C, Maher ER: Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 2001, 69(1):49-54.
- [6]Niemann S, Muller U: Mutations in SDHC cause autosomal dominant paraganglioma, type 3. Nat Genet 2000, 26(3):268-270.
- [7]Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, Devilee P, Cremers CW, Schiffman JD, Bentz BG, Gygi SP, Winge DR, Kremer H, Rutter J: SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science 2009, 325(5944):1139-1142.
- [8]Burnichon N, Briere JJ, Libe R, Vescovo L, Riviere J, Tissier F, Jouanno E, Jeunemaitre X, Benit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP: SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet 2010, 19(15):3011-3020.
- [9]Van der Mey AG, Maaswinkel-Mooy PD, Cornelisse CJ, Schmidt PH, van de Kamp JJ: Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory. Lancet 1989, 2(8675):1291-1294.
- [10]Comino-Méndez I, Gracia-Aznárez FJ, Schiavi F, Landa I, Leandro-García LJ, Letón R, Honrado E, Ramos-Medina R, Caronia D, Pita G, Gómez-Graña A, de Cubas AA, Inglada-Pérez L, Maliszewska A, Taschin E, Bobisse S, Pica G, Loli P, Hernández-Lavado R, Díaz JA, Gómez-Morales M, González-Neira A, Roncador G, Rodríguez-Antona C, Benítez J, Mannelli M, Opocher G, Robledo M, Cascón A: Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 2011, 43(7):663-667.
- [11]Pigny P, Vincent A, Cardot BC, Bertrand M, de M,V, Crepin M, Porchet N, Caron P: Paraganglioma after maternal transmission of a succinate dehydrogenase gene mutation. J Clin Endocrinol Metab 2008, 93(5):1609-1615.
- [12]Neumann HP, Erlic Z: Maternal transmission of symptomatic disease with SDHD mutation: fact or fiction? J Clin Endocrinol Metab 2008, 93(5):1573-1575.
- [13]Yeap PM, Tobias ES, Mavraki E, Fletcher A, Bradshaw N, Freel EM, Cooke A, Murday VA, Davidson HR, Perry CG, Lindsay RS: Molecular analysis of pheochromocytoma after maternal transmission of SDHD mutation elucidates mechanism of parent-of-origin effect. J Clin Endocrinol Metab 2011, 96(12):E2009-E2013.
- [14]Douwes Dekker PB, Corver WE, Hogendoorn PC, Van Der Mey AG, Cornelisse CJ: Multiparameter DNA flow-sorting demonstrates diploidy and SDHD wild-type gene retention in the sustentacular cell compartment of head and neck paragangliomas: chief cells are the only neoplastic component. J Pathol 2004, 202(4):456-462.
- [15]Devilee P, van Schothorst EM, Bardoel AF, Bonsing B, Kuipers-Dijkshoorn N, James MR, Fleuren G, Van Der Mey AG, Cornelisse CJ: Allelotype of head and neck paragangliomas: allelic imbalance is confined to the long arm of chromosome 11, the site of the predisposing locus PGL. Genes Chromosomes Cancer 1994, 11(2):71-78.
- [16]van Nederveen FH, Gaal J, Favier J, Korpershoek E, Oldenburg RA, de Bruyn EM, Sleddens HF, Derkx P, Rivière J, Dannenberg H, Petri BJ, Komminoth P, Pacak K, Hop WC, Pollard PJ, Mannelli M, Bayley JP, Perren A, Niemann S, Verhofstad AA, de Bruïne AP, Maher ER, Tissier F, Méatchi T, Badoual C, Bertherat J, Amar L, Alataki D, Van Marck E, Ferrau F, et al.: An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol 2009, 10(8):764-771.
- [17]Baysal BE, McKay SE, Kim YJ, Zhang Z, Alila L, Willett-Brozick JE, Pacak K, Kim TH, Shadel GS: Genomic imprinting at a boundary element flanking the SDHD locus. Hum Mol Genet 2011, 20(22):4452-4461.
- [18]Hensen EF, Jordanova ES, van Minderhout IJHM, Hogendoorn PCW, Taschner PEM, van der Mey AGL, Devilee P, Cornelisse CJ: Somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene 2004, 23(23):4076-4083.
- [19]Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Pequignot E, Munnich A, Rotig A: Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet 1995, 11(2):144-149.
- [20]Bayley JP, van M,I, Hogendoorn PC, Cornelisse CJ, van der Wal A, Prins FA, Teppema L, Dahan A, Devilee P, Taschner PE: Sdhd and SDHD/H19 knockout mice do not develop paraganglioma or pheochromocytoma. PLoS One 2009, 4(11):e7987.
- [21]Piruat JI, Pintado CO, Ortega-Saenz P, Roche M, Lopez-Barneo J: The mitochondrial SDHD gene is required for early embryogenesis, and its partial deficiency results in persistent carotid body glomus cell activation with full responsiveness to hypoxia. Mol Cell Biol 2004, 24(24):10933-10940.
- [22]Beristain E, Vicente MA, Guerra I, Gutierrez-Corres FB, Garin I, de Perez NG: Disomy as the genetic underlying mechanisms of loss of heterozigosity in SDHD-paragangliomas. J Clin Endocrinol Metab 2013, 98(5):E1012-E1016.
- [23]Dannenberg H, de Krijger RR, Zhao J, Speel EJ, Saremaslani P, Dinjens WN, Mooi WJ, Roth J, Heitz PU, Komminoth P: Differential loss of chromosome 11q in familial and sporadic parasympathetic paragangliomas detected by comparative genomic hybridization. Am J Pathol 2001, 158(6):1937-1942.
- [24]Riemann K, Sotlar K, Kupka S, Braun S, Zenner HP, Preyer S, Pfister M, Pusch CM, Blin N: Chromosome 11 monosomy in conjunction with a mutated SDHD initiation codon in nonfamilial paraganglioma cases. Cancer Genet Cytogenet 2004, 150(2):128-135.
- [25]Margetts CDE, Astuti D, Gentle DC, Cooper WN, Cascon A, Catchpoole D, Robledo M, Neumann HPH, Latif F, Maher ER: Epigenetic analysis of HIC1, CASP8, FLIP, TSP1, DCR1, DCR2, DR4, DR5, KvDMR1, H19 and preferential 11p15.5 maternal-allele loss in von Hippel-Lindau and sporadic phaeochromocytomas. Endocr Relat Cancer 2005, 12(1):161-172.
- [26]Mircescu H, Wilkin F, Paquette J, Oligny LL, Decaluwe H, Gaboury L, Nolet S, Van VG, Deal C: Molecular characterization of a pediatric pheochromocytoma with suspected bilateral disease. J Pediatr 2001, 138(2):269-273.