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High-resolution genomic profiling of an adult Wilms’ tumor: evidence for a pathogenesis distinct from corresponding pediatric tumors

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Abstract

Wilms’ tumor (WT), the most common kidney tumor among children, is characterized by a triphasic morphology consisting of blastemal, epithelial, and stromal components. Adult WT is a rare malignancy displaying similar histological features. We here present the first published high-resolution genomic analysis of a mixed-type adult WT. This revealed a more pronounced genetic complexity than usually observed in children with mixed-type WT. The majority of chromosomes displayed uniparental disomies, and microdeletions were present in genes with known importance for tumor formation (LRP1B, FHIT, and WWOX) or organogenesis (NEGR1 and ZFPM2), abnormalities not previously reported for pediatric WT. Our results indicate that adult WT is a biological entity distinct from the corresponding pediatric tumor type.

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References

  1. Davidoff AM (2009) Wilms’ tumor. Curr Opin Pediatr 21(3):357–364. doi:PAS.0b013e31802bdd56/MOP.0b013e32832b323a

    Article  PubMed  Google Scholar 

  2. Terenziani M, Spreafico F, Collini P, Piva L, Perotti D, Podda M, Gandola L, Massimino M, Cereda S, Cefalo G, Luksch R, Casanova M, Ferrari A, Polastri D, Valagussa P, Fossati-Bellani F (2004) Adult Wilms’ tumor: a monoinstitutional experience and a review of the literature. Cancer 101(2):289–293. doi:jcp./cncr.20387

    Article  PubMed  Google Scholar 

  3. Reinhard H, Aliani S, Ruebe C, Stockle M, Leuschner I, Graf N (2004) Wilms’ tumor in adults: results of the society of pediatric oncology (SIOP) 93-01/society for pediatric oncology and hematology (GPOH) study. J Clin Oncol 22(22):4500–4506. doi:10.1200/JCO.2004.12.099

    Article  PubMed  Google Scholar 

  4. Grundy PE, Breslow NE, Li S, Perlman E, Beckwith JB, Ritchey ML, Shamberger RC, Haase GM, D’Angio GJ, Donaldson M, Coppes MJ, Malogolowkin M, Shearer P, Thomas PR, Macklis R, Tomlinson G, Huff V, Green DM (2005) Loss of heterozygosity for chromosomes 1p and 16q is an adverse prognostic factor in favorable-histology Wilms tumor: a report from the national wilms tumor study group. J Clin Oncol 23(29):7312–7321. doi:10.1200/JCO.2005.01.2799

    Article  PubMed  CAS  Google Scholar 

  5. Hing S, Lu YJ, Summersgill B, King-Underwood L, Nicholson J, Grundy P, Grundy R, Gessler M, Shipley J, Pritchard-Jones K (2001) Gain of 1q is associated with adverse outcome in favorable histology Wilms’ tumors. Am J Pathol 158(2):393–398. doi:10.1016/S0002-9440(10)63982-X

    Article  PubMed  CAS  Google Scholar 

  6. Wittmann S, Zirn B, Alkassar M, Ambros P, Graf N, Gessler M (2007) Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis. Genes Chrom Cancer 46(2):163–170. doi:jcp./gcc.20397

    Article  PubMed  CAS  Google Scholar 

  7. Powlesland RM, Charles AK, Malik KT, Reynolds PA, Pires S, Boavida M, Brown KW (2000) Loss of heterozygosity at 7p in Wilms’ tumour development. Br J Cancer 82(2):323–329. doi:10.1054/bjoc.1999.0922

    Article  PubMed  CAS  Google Scholar 

  8. Kaneko Y, Homma C, Maseki N, Sakurai M, Hata J (1991) Correlation of chromosome abnormalities with histological and clinical features in Wilms’ and other childhood renal tumors. Cancer Res 51(21):5937–5942

    PubMed  CAS  Google Scholar 

  9. Gillis AJ, Oosterhuis JW, Schipper ME, Barten EJ, van Berlo R, van Gurp RJ, Abraham M, Saunders GF, Looijenga LH (1994) Origin and biology of a testicular Wilms’ tumor. Genes Chrom Cancer 11(2):126–135

    Article  PubMed  CAS  Google Scholar 

  10. Li P, Perle MA, Scholes JV, Yang GC (2002) Wilms’ tumor in adults: aspiration cytology and cytogenetics. Diagn Cytopathol 26(2):99–103. doi:jcp./dc.10048

    Article  PubMed  CAS  Google Scholar 

  11. Rubin BP, Pins MR, Nielsen GP, Rosen S, Hsi BL, Fletcher JA, Renshaw AA (2000) Isochromosome 7q in adult Wilms’ tumors: diagnostic and pathogenetic implications. Am J Surg Pathol 24(12):1663–1669

    Article  PubMed  CAS  Google Scholar 

  12. Fletcher JA, Renshaw AA (1996) Isochromosome 7q in adult Wilms’ tumor. Cancer Genet Cytogenet 86(2):168–169. doi:0165-4608(95)00172-7

    Article  PubMed  CAS  Google Scholar 

  13. Sherwood JB, Bard R, Bhargava M, Burns ER, Iqbal MA (1989) A human adult Wilms’ tumor. Histologic, ultrastructural, and cytogenetic analysis. Cancer Genet Cytogenet 42(1):35–42. doi:0165-4608(89)90005-8

    Article  PubMed  CAS  Google Scholar 

  14. Sheng WW, Soukup S, Bove K, Gotwals B, Lampkin B (1990) Chromosome analysis of 31 Wilms’ tumors. Cancer Res 50(9):2786–2793

    PubMed  CAS  Google Scholar 

  15. Tawil A, Cox JN, Roth AD, Briner J, Droz JP, Remadi S (1999) Wilms’ tumor in the adult—report of a case and review of the literature. Pathol Res Pract 195(2):105–111, discussion 113–104

    PubMed  CAS  Google Scholar 

  16. Izawa JI, Al-Omar M, Winquist E, Stitt L, Rodrigues G, Steele S, Siemens DR, Luke PP (2008) Prognostic variables in adult Wilms tumour. Can J Surg 51(4):252–256

    PubMed  Google Scholar 

  17. Dahlen A, Debiec-Rychter M, Pedeutour F, Domanski HA, Hoglund M, Bauer HC, Rydholm A, Sciot R, Mandahl N, Mertens F (2003) Clustering of deletions on chromosome 13 in benign and low-malignant lipomatous tumors. Int J Cancer 103(5):616–623. doi:jcp./ijc.10864

    Article  PubMed  CAS  Google Scholar 

  18. Staaf J, Lindgren D, Vallon-Christersson J, Isaksson A, Goransson H, Juliusson G, Rosenquist R, Hoglund M, Borg A, Ringner M (2008) Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays. Genome Biol 9(9):R136. doi:10.1186/gb-2008-9-9-r136

    Article  PubMed  Google Scholar 

  19. Adsay NV, Eble JN, Srigley JR, Jones EC, Grignon DJ (2000) Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 24(7):958–970

    Article  PubMed  CAS  Google Scholar 

  20. Michal M, Hes O, Bisceglia M, Simpson RH, Spagnolo DV, Parma A, Boudova L, Hora M, Zachoval R, Suster S (2004) Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch 445(4):359–367. doi:10.1007/s00428-004-1060-y

    Article  PubMed  Google Scholar 

  21. Turbiner J, Amin MB, Humphrey PA, Srigley JR, De Leval L, Radhakrishnan A, Oliva E (2007) Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. Am J Surg Pathol 31(4):489–500. doi:10.1097/PAS.0b013e31802bdd5600000478-200704000-00001

    Article  PubMed  Google Scholar 

  22. Smith DI, Zhu Y, McAvoy S, Kuhn R (2006) Common fragile sites, extremely large genes, neural development and cancer. Cancer Lett 232(1):48–57. doi:10.1016/j.canlet.2005.06.049

    Article  PubMed  CAS  Google Scholar 

  23. Prazeres H, Torres J, Rodrigues F, Pinto M, Pastoriza MC, Gomes D, Cameselle-Teijeiro J, Vidal A, Martins TC, Sobrinho-Simoes M, Soares P (2010) Chromosomal, epigenetic and microRNA-mediated inactivation of LRP1B, a modulator of the extracellular environment of thyroid cancer cells. Oncogene. doi:10.1038/onc.2010.512

  24. Zanesi N, Fidanza V, Fong LY, Mancini R, Druck T, Valtieri M, Rudiger T, McCue PA, Croce CM, Huebner K (2001) The tumor spectrum in FHIT-deficient mice. Proc Natl Acad Sci USA 98(18):10250–10255. doi:10.1073/pnas.191345898 191345898

    Article  PubMed  CAS  Google Scholar 

  25. Aqeilan RI, Croce CM (2007) WWOX in biological control and tumorigenesis. J Cell Physiol 212(2):307–310. doi:10.1002/jcp. 21099

    Article  PubMed  CAS  Google Scholar 

  26. Marg A, Sirim P, Spaltmann F, Plagge A, Kauselmann G, Buck F, Rathjen FG, Brummendorf T (1999) Neurotractin, a novel neurite outgrowth-promoting Ig-like protein that interacts with CEPU-1 and LAMP. J Cell Biol 145(4):865–876

    Article  PubMed  CAS  Google Scholar 

  27. Schafer M, Brauer AU, Savaskan NE, Rathjen FG, Brummendorf T (2005) Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive astrocytes after entorhinal cortex lesion. Mol Cell Neurosci 29(4):580–590. doi:10.1016/j.mcn.2005.04.010

    Article  PubMed  Google Scholar 

  28. Jack BH, Crossley M (2010) GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis. J Biol Chem 285, 2010/08/14 edn. doi:M110.141317 [pii] 10.1074/jbc.M110.141317

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Acknowledgments

We are grateful for the technical assistance of the Swegene Centre for Integrative Biology at Lund University (SCIBLU). We would also like to thank our grant sponsors, namely, Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, Crafoord Foundation, Gunnar Nilsson Cancer Foundation, the Royal Physiographic Society, and the Medical Faculty at Lund University.

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Authors and Affiliations

  1. Department of Clinical Genetics, BMC B13, University and Regional Laboratories, Lund University, 221 84, Lund, Sweden

    Jenny Karlsson, Linda Holmquist Mengelbier & David Gisselsson Nord

  2. Department of Urology, Skåne University Hospital, Malmö, Sweden

    Peter Elfving

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  1. Jenny Karlsson
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  2. Linda Holmquist Mengelbier
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  3. Peter Elfving
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  4. David Gisselsson Nord
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Correspondence to Jenny Karlsson.

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Karlsson, J., Holmquist Mengelbier, L., Elfving, P. et al. High-resolution genomic profiling of an adult Wilms’ tumor: evidence for a pathogenesis distinct from corresponding pediatric tumors. Virchows Arch 459, 547–553 (2011). https://doi.org/10.1007/s00428-011-1148-0

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  • DOI: https://doi.org/10.1007/s00428-011-1148-0

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