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Open Access 01-12-2004 | Research article

No evidence for involvement of SDHD in neuroblastoma pathogenesis

Authors: Katleen De Preter, Jo Vandesompele, Jasmien Hoebeeck, Caroline Vandenbroecke, Jöel Smet, Annick Nuyts, Geneviève Laureys, Valérie Combaret, Nadine Van Roy, Frank Roels, Rudy Van Coster, Marleen Praet, Anne De Paepe, Frank Speleman

Published in: BMC Cancer | Issue 1/2004

Abstract

Background

Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma.

Methods

SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria.

Results

Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype.

Conclusions

Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis.

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Cooper MJ, Hutchins GM, Cohen PS, Helman LJ, Mennie RJ, Israel MA: Human neuroblastoma tumor cell lines correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts. Cell Growth Differ. 1990, 1: 149-59.PubMed

Bown N, Cotterill S, Lastowska M, O'Neill S, Pearson AD, Plantaz D, Meddeb M, Danglot G, Brinkschmidt C, Christiansen H, et al: Gain of chromosome arm 17q and adverse outcome in patients with neuroblastoma. N Engl J Med. 1999, 340: 1954-61. 10.1056/NEJM199906243402504.CrossRefPubMed

Maris JM, Matthay KK: Molecular biology of neuroblastoma. J Clin Oncol. 1999, 17: 2264-79.PubMed

Brodeur GM: Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003, 3: 203-16. 10.1038/nrc1014.CrossRefPubMed

Plantaz D, Vandesompele J, Van Roy N, Lastowska M, Bown N, Combaret V, Favrot MC, Delattre O, Michon J, Benard J, et al: Comparative genomic hybridization (CGH) analysis of stage 4 neuroblastoma reveals high frequency of 11q deletion in tumors lacking MYCN amplification. Int J Cancer. 2001, 91: 680-6. 10.1002/1097-0215(200002)9999:9999<::AID-IJC1114>3.0.CO;2-R.CrossRefPubMed

Vandesompele J, Van Roy N, Van Gele M, Laureys G, Ambros P, Heimann P, Devalck C, Schuuring E, Brock P, Otten J, et al: Genetic heterogeneity of neuroblastoma studied by comparative genomic hybridization. Genes Chromosomes Cancer. 1998, 23: 141-52. 10.1002/(SICI)1098-2264(199810)23:2<141::AID-GCC7>3.0.CO;2-2.CrossRefPubMed

Vandesompele J, Speleman F, Van Roy N, Laureys G, Brinskchmidt C, Christiansen H, Lampert F, Lastowska M, Bown N, Pearson A, et al: Multicentre analysis of patterns of DNA gains and losses in 204 neuroblastoma tumors: how many genetic subgroups are there?. Med Pediatr Oncol. 2001, 36: 5-10. 10.1002/1096-911X(20010101)36:1<5::AID-MPO1003>3.0.CO;2-E.CrossRefPubMed

Luttikhuis ME, Powell JE, Rees SA, Genus T, Chughtai S, Ramani P, Mann JR, McConville CM: Neuroblastomas with chromosome 11q loss and single copy MYCN comprise a biologically distinct group of tumours with adverse prognosis. Br J Cancer. 2001, 85: 531-7. 10.1054/bjoc.2001.1960.CrossRefPubMedPubMedCentral

Breen CJ, O'Meara A, McDermott M, Mullarkey M, Stallings RL: Coordinate deletion of chromosome 3p and 11q in neuroblastoma detected by comparative genomic hybridization. Cancer Genet Cytogenet. 2000, 120: 44-9. 10.1016/S0165-4608(99)00252-6.CrossRefPubMed

10.

Srivatsan ES, Murali V, Seeger RC: Loss of heterozygosity for alleles on chromosomes 11q and 14q in neuroblastoma. Prog Clin Biol Res. 1991, 366: 91-8.PubMed

11.

Maris JM, Guo C, White PS, Hogarty MD, Thompson PM, Stram DO, Gerbing R, Matthay KK, Seeger RC, Brodeur GM: Allelic deletion at chromosome bands 11q14-23 is common in neuroblastoma. Med Pediatr Oncol. 2001, 36: 24-7. 10.1002/1096-911X(20010101)36:1<24::AID-MPO1007>3.0.CO;2-7.CrossRefPubMed

12.

Vandesompele J, Baudis M, De Preter K, Van Roy N, Ambros P, Bown N, Combaret V, Lastowska M, Nicholson JC, O'Meara A, et al: Unequivocal delineation of clinico-genetic subgroups and identification of a long term survivor signature for neuroblastoma. J Clin Oncol.

13.

Spitz R, Hero B, Ernestus K, Berthold F: Deletions in chromosome arms 3p and 11q are new prognostic markers in localized and 4s neuroblastoma. Clin Cancer Res. 2003, 9: 52-8.PubMed

14.

Bader SA, Fasching C, Brodeur GM, Stanbridge EJ: Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells. Cell Growth Differ. 1991, 2: 245-55.PubMed

15.

Guo C, White PS, Hogarty MD, Brodeur GM, Gerbing R, Stram DO, Maris JM: Deletion of 11q23 is a frequent event in the evolution of MYCN single-copy high-risk neuroblastomas. Med Pediatr Oncol. 2000, 35: 544-6. 10.1002/1096-911X(20001201)35:6<544::AID-MPO10>3.0.CO;2-2.CrossRefPubMed

16.

Guo C, White PS, Weiss MJ, Hogarty MD, Thompson PM, Stram DO, Gerbing R, Matthay KK, Seeger RC, Brodeur GM, et al: Allelic deletion at 11q23 is common in MYCN single copy neuroblastomas. Oncogene. 1999, 18: 4948-57. 10.1038/sj.onc.1202887.CrossRefPubMed

17.

Hirawake H, Taniwaki M, Tamura A, Amino H, Tomitsuka E, Kita K: Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase. Biochim Biophys Acta. 1999, 1412: 295-300. 10.1016/S0005-2728(99)00071-7.CrossRefPubMed

18.

Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K: Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23. Cytogenet Cell Genet. 1997, 79: 132-8.CrossRefPubMed

19.

Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, et al: Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000, 287: 848-51. 10.1126/science.287.5454.848.CrossRefPubMed

20.

Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, et al: Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 2002, 346: 1459-66. 10.1056/NEJMoa020152.CrossRefPubMed

21.

Gimm O, Armanios M, Dziema H, Neumann HP, Eng C: Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. Cancer Res. 2000, 60: 6822-5.PubMed

22.

Badenhop RF, Cherian S, Lord RS, Baysal BE, Taschner PE, Schofield PR: Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss. Genes Chromosomes Cancer. 2001, 31: 255-63. 10.1002/gcc.1142.CrossRefPubMed

23.

Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A, Jeunemaitre X: The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet. 2001, 69: 1186-97. 10.1086/324413.CrossRefPubMedPubMedCentral

24.

Baysal BE, Willett-Brozick JE, Lawrence EC, Drovdlic CM, Savul SA, McLeod DR, Yee HA, Brackmann DE, Slattery WH, Myers EN, et al: Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet. 2002, 39: 178-83. 10.1136/jmg.39.3.178.CrossRefPubMedPubMedCentral

25.

Aguiar RC, Cox G, Pomeroy SL, Dahia PL: Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas. J Clin Endocrinol Metab. 2001, 86: 2890-4. 10.1210/jc.86.6.2890.PubMed

26.

Masuoka J, Brandner S, Paulus W, Soffer D, Vital A, Chimelli L, Jouvet A, Yonekawa Y, Kleihues P, Ohgaki H: Germline SDHD mutation in paraganglioma of the spinal cord. Oncogene. 2001, 20: 5084-6. 10.1038/sj.onc.1204579.CrossRefPubMed

27.

Kytola S, Nord B, Elder EE, Carling T, Kjellman M, Cedermark B, Juhlin C, Hoog A, Isola J, Larsson C: Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas. Genes Chromosomes Cancer. 2002, 34: 325-32. 10.1002/gcc.10081.CrossRefPubMed

28.

Taschner PE, Jansen JC, Baysal BE, Bosch A, Rosenberg EH, Brocker-Vriends AH, van Der Mey AG, van Ommen GJ, Cornelisse CJ, Devilee P: Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene. Genes Chromosomes Cancer. 2001, 31: 274-81. 10.1002/gcc.1144.CrossRefPubMed

29.

Jogi A, Ora I, Nilsson H, Lindeheim A, Makino Y, Poellinger L, Axelson H, Pahlman S: Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci U S A. 2002, 99: 7021-6. 10.1073/pnas.102660199.CrossRefPubMedPubMedCentral

30.

Schleiermacher G, Janoueix-Lerosey I, Combaret V, Derre J, Couturier J, Aurias A, Delattre O: Combined 24-color karyotyping and comparative genomic hybridization analysis indicates predominant rearrangements of early replicating chromosome regions in neuroblastoma. Cancer Genet Cytogenet. 2003, 141: 32-42. 10.1016/S0165-4608(02)00644-1.CrossRefPubMed

31.

Van Roy N, Van Limbergen H, Vandesompele J, Van Gele M, Poppe B, Salwen H, Laureys G, Manoel N, De Paepe A, Speleman F: Combined M-FISH and CGH analysis allows comprehensive description of genetic alterations in neuroblastoma cell lines. Genes Chromosomes Cancer. 2001, 32: 126-35. 10.1002/gcc.1174.CrossRefPubMed

32.

Van Roy N, Jauch A, Van Gele M, Laureys G, Versteeg R, De Paepe A, Cremer T, Speleman F: Comparative genomic hybridization analysis of human neuroblastomas: detection of distal 1p deletions and further molecular genetic characterization of neuroblastoma cell lines. Cancer Genet Cytogenet. 1997, 97: 135-42. 10.1016/S0165-4608(96)00362-7.CrossRefPubMed

33.

De Preter K, Speleman F, Combaret V, Lunec J, Laureys G, Eussen BH, Francotte N, Board J, Pearson AD, De Paepe A, et al: Quantification of MYCN, DDX1, and NAG gene copy number in neuroblastoma using a real-time quantitative PCR assay. Mod Pathol. 2002, 15: 159-66. 10.1038/modpathol.3880508.CrossRefPubMed

34.

Van Roy N, Laureys G, Cheng NC, Willem P, Opdenakker G, Versteeg R, Speleman F: 1;17 translocations and other chromosome 17 rearrangements in human primary neuroblastoma tumors and cell lines. Genes Chromosomes Cancer. 1994, 10: 103-14.CrossRefPubMed

35.

Devilee P, Cleton-Jansen AM, Cornelisse CJ: Ever since Knudson. Trends Genet. 2001, 17: 569-73. 10.1016/S0168-9525(01)02416-7.CrossRefPubMed

36.

Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB: Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A. 1996, 93: 9821-6. 10.1073/pnas.93.18.9821.CrossRefPubMedPubMedCentral

37.

Li LC, Dahiya R: MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002, 18: 1427-31. 10.1093/bioinformatics/18.11.1427.CrossRefPubMed

38.

Vandesompele J, De Paepe A, Speleman F: Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal Biochem. 2002, 303: 95-8. 10.1006/abio.2001.5564.CrossRefPubMed

39.

De Preter K, Vandesompele J, Heimann P, Kockx MM, Van Gele M, Hoebeeck J, De Smet E, Demarche M, Laureys G, Van Roy N, et al: Application of laser capture microdissection in genetic analysis of neuroblastoma and neuroblastoma precursor cells. Cancer Lett. 2003, 197: 53-61. 10.1016/S0304-3835(03)00084-3.CrossRefPubMed

40.

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3:RESEARCH0034: 1-11.

41.

Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, Munnich A: Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta. 1994, 228: 35-51. 10.1016/0009-8981(94)90055-8.CrossRefPubMed

42.

Van Coster R, Smet J, George E, De Meirleir L, Seneca S, Van Hove J, Sebire G, Verhelst H, De Bleecker J, Van Vlem B, et al: Blue native polyacrylamide gel electrophoresis: a powerful tool in diagnosis of oxidative phosphorylation defects. Pediatr Res. 2001, 50: 658-65.CrossRefPubMed

43.

Cascon A, Ruiz-Llorente S, Cebrian A, Leton R, Telleria D, Benitez J, Robledo M: G12S and H50R variations are polymorphisms in the SDHD gene. Genes Chromosomes Cancer. 2003, 37: 220-221. 10.1002/gcc.10212.CrossRefPubMed

44.

Cascon A, Ruiz-Llorente S, Cebrian A, Telleria D, Rivero JC, Diez JJ, Lopez-Ibarra PJ, Jaunsolo MA, Benitez J, Robledo M: Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma. Eur J Hum Genet. 2002, 10: 457-61. 10.1038/sj.ejhg.5200829.CrossRefPubMed

45.

Lima J, Maximo V, Soares P, Sobrinho-Simoes M: Alterations of the SDHD gene locus in midgut carcinoids. Genes Chromosomes Cancer. 2003, 36: 424-10.1002/gcc.10147.CrossRefPubMed

46.

Dannenberg H, Dinjens WN, Abbou M, Van Urk H, Pauw BK, Mouwen D, Mooi WJ, de Krijger RR: Frequent germ-line succinate dehydrogenase subunit D gene mutations in patients with apparently sporadic parasympathetic paraganglioma. Clin Cancer Res. 2002, 8: 2061-6.PubMed

47.

Hui AB, Lo KW, Chan SY, Kwong J, Chan AS, Huang DP: Absence of SDHD mutations in primary nasopharyngeal carcinomas. Int J Cancer. 2002, 97: 875-7. 10.1002/ijc.10066.CrossRefPubMed

48.

Douwes Dekker PB, Hogendoorn PC, Kuipers-Dijkshoorn N, Prins FA, van Duinen SG, Taschner PE, van der Mey AG, Cornelisse CJ: SDHD mutations in head and neck paragangliomas result in destabilization of complex II in the mitochondrial respiratory chain with loss of enzymatic activity and abnormal mitochondrial morphology. J Pathol. 2003, 201: 480-6. 10.1002/path.1461.CrossRefPubMed

49.

Takahashi H, Ikuta F, Tsuchida T, Tanaka R: Ultrastructural alterations of neuronal cells in a brain stem ganglioglioma. Acta Neuropathol (Berl). 1987, 74: 307-12.CrossRef

50.

Taxy JB: Electron microscopy in the diagnosis of neuroblastoma. Arch Pathol Lab Med. 1980, 104: 355-60.PubMed

51.

Staley NA, Poleksy HF, Bensch KG: Fine structural and biochemical studies on the malignant ganglioneuroma. J Neuropathol Exp Neurol. 1967, 26: 634-53.CrossRefPubMed

52.

Mackay B, Masse SR, King OY, Butler J: Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates. Pediatrics. 1975, 56: 1045-9.PubMed

53.

Misugi K, Misugi N, Newton WA: Fine structural study of neuroblastoma, ganglioneuroblastoma, and pheochromocytoma. Arch Pathol. 1968, 86: 160-70.PubMed

54.

Yankovskaya V, Horsefield R, Tornroth S, Luna-Chavez C, Miyoshi H, Leger C, Byrne B, Cecchini G, Iwata S: Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 2003, 299: 700-4. 10.1126/science.1079605.CrossRefPubMed

55.

Habano W, Sugai T, Nakamura S, Uesugi N, Higuchi T, Terashima M, Horiuchi S: Reduced expression and loss of heterozygosity of the SDHD gene in colorectal and gastric cancer. Oncol Rep. 2003, 10: 1375-80.PubMed

56.

Hackenbrock CR, Rehn TG, Weinbach EC, Lemasters JJ: Oxidative phosphorylation and ultrastructural transformation in mitochondria in the intact ascites tumor cell. J Cell Biol. 1971, 51: 123-37. 10.1083/jcb.51.1.123.CrossRefPubMedPubMedCentral

57.

Ord MJ, Smith RA: Correlation of mitochondrial form and function in vivo: microinjection of substrate and nucleotides. Cell Tissue Res. 1982, 227: 129-37. 10.1007/BF00206336.CrossRefPubMed

58.

Gottlieb E, Armour SM, Harris MH, Thompson CB: Mitochondrial membrane potential regulates matrix configuration and cytochrome c release during apoptosis. Cell Death Differ. 2003, 10: 709-17. 10.1038/sj.cdd.4401231.CrossRefPubMed

59.

van Loo G, Saelens X, van Gurp M, MacFarlane M, Martin SJ, Vandenabeele P: The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet. Cell Death Differ. 2002, 9: 1031-42. 10.1038/sj.cdd.4401088.CrossRefPubMed

60.

Ravagnan L, Roumier T, Kroemer G: Mitochondria, the killer organelles and their weapons. J Cell Physiol. 2002, 192: 131-7. 10.1002/jcp.10111.CrossRefPubMed

61.

Pietenpol JA, Bohlander SK, Sato Y, Papadopoulos N, Liu B, Friedman C, Trask BJ, Roberts JM, Kinzler KW, Rowley JD, et al: Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias. Cancer Res. 1995, 55: 1206-10.PubMed

62.

Fero ML, Randel E, Gurley KE, Roberts JM, Kemp CJ: The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature. 1998, 396: 177-80. 10.1038/24179.CrossRefPubMed

63.

Venkatachalam S, Shi YP, Jones SN, Vogel H, Bradley A, Pinkel D, Donehower LA: Retention of wild-type p53 in tumors from p53 heterozygous mice: reduction of p53 dosage can promote cancer formation. Embo J. 1998, 17: 4657-67. 10.1093/emboj/17.16.4657.CrossRefPubMedPubMedCentral

64.

Inoue K, Zindy F, Randle DH, Rehg JE, Sherr CJ: Dmp1 is haplo-insufficient for tumor suppression and modifies the frequencies of Arf and p53 mutations in Myc-induced lymphomas. Genes Dev. 2001, 15: 2934-9. 10.1101/gad.929901.CrossRefPubMedPubMedCentral

65.

Kwabi-Addo B, Giri D, Schmidt K, Podsypanina K, Parsons R, Greenberg N, Ittmann M: Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression. Proc Natl Acad Sci U S A. 2001, 98: 11563-8. 10.1073/pnas.201167798.CrossRefPubMedPubMedCentral

66.

Yan H, Dobbie Z, Gruber SB, Markowitz S, Romans K, Giardiello FM, Kinzler KW, Vogelstein B: Small changes in expression affect predisposition to tumorigenesis. Nat Genet. 2002, 30: 25-6. 10.1038/ng799.CrossRefPubMed

67.

Magee JA, Abdulkadir SA, Milbrandt J: Haploinsufficiency at the Nkx3.1 locus. A paradigm for stochastic, dosage-sensitive gene regulation during tumor initiation. Cancer Cell. 2003, 3: 273-83. 10.1016/S1535-6108(03)00047-3.CrossRefPubMed

68.

Quon KC, Berns A: Haplo-insufficiency? Let me count the ways. Genes Dev. 2001, 15: 2917-21. 10.1101/gad.949001.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/4/55/prepub

Title: No evidence for involvement of SDHD in neuroblastoma pathogenesis
Authors: Katleen De Preter
Jo Vandesompele
Jasmien Hoebeeck
Caroline Vandenbroecke
Jöel Smet
Annick Nuyts
Geneviève Laureys
Valérie Combaret
Nadine Van Roy
Frank Roels
Rudy Van Coster
Marleen Praet
Anne De Paepe
Frank Speleman
Publication date: 01-12-2004
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2004
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-4-55

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