Top

Published in:

01-08-2006 | Original Article

Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes

Authors: Barbara Guertl, Ivo Leuschner, Dieter Harms, Gerald Hoefler

Published in: Virchows Archiv | Issue 2/2006

Abstract

Nephroblastomas are embryonal tumors exhibiting a wide variety of different morphological features and genetic changes. Some of the genetic aberrations were associated with a certain histological subtype. It is generally assumed that nephroblastomas develop as subclonal proliferations from nephrogenic rests. However, so far, a very limited amount of tumors from only part of the morphological spectrum of nephroblastomas was investigated. We therefore investigated the clonality of 45 tumors of all different histological subtypes. The number of each subtype was in accordance with the percentage of occurrence of the respective subtype. We analyzed a highly polymorphic locus of the human androgen receptor gene for nonrandom X-inactivation of genomic DNA using a methylation-sensitive restriction enzyme. Data were obtained for 39 tumors. Eighteen of the tumors included were noninformative in the genetic locus examined, the remaining 21 tumors were monoclonal regardless of the histological subtype. Our findings therefore support the hypothesis that Wilms’ tumors are monoclonal proliferations despite their large variety of morphological features.

Astuti D, DaSilva NF, Dallol A, Gentle D, Martinsson T, Kogner P, Grundy R, Kishida T, Yao M, Latif F, Maher ER (2004) SLIT2 promoter methylation analysis in neuroblastoma, Wilms’ tumour and renal cell carcinoma. Br J Cancer 90:515–521CrossRefPubMed

Bardeesy N, Falkoff D, Petruzzi MJ, Nowak N, Zabel B, Adam M, Aguiar MC, Grundy P, Shows T, Pelletier J (1994) Anaplastic Wilms’ tumour, a subtype displaying poor prognosis, harbours p53 gene mutations. Nat Genet 7:91–97CrossRefPubMed

Bardeesy N, Beckwith JB, Pelletier J (1995) Clonal expansion and attenuated apoptosis in Wilms’ tumor are associated with p53 gene mutations. Cancer Res 55:215–219PubMed

Beckwith JB (1993) Precursor lesions of Wilms tumor: clinical and biological implications. Med Pediatr Oncol 21:178–181CrossRef

Beckwith JB, Kiviat NB, Bonadio JF (1990) Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms’ tumor. Pediatr Pathol 10:1–36PubMedCrossRef

Boily G, Saikali Z, Sinnett D (2004) Methylation analysis of the glypican 3 gene in embryonal tumours. Br J Cancer 90:1606–1611CrossRefPubMed

Breslow NE, Olshan A, Beckwith JB, Green DM (1993) Epidemiology of Wilms tumor. Med Pediatr Oncol 21:178–181CrossRef

Breslow NE, Olson J, Moksness J, Beckwith JB, Grundy P (1996) Familial Wilms’ tumor: a descriptive study. Med Pediatr Oncol 27:398–403CrossRefPubMed

Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C, Housman DE (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520CrossRefPubMed

10.

Charles AK, Brown KW, Berry PJ (1998) Microdissecting the genetic events in nephrogenic rests and Wilms tumor development. Am J Pathol 153:991–1000PubMed

11.

Faria P, Beckwith JB, Mishra K, Zuppan C, Weeks DA, Breslow N, Green DM (1996) Focal versus diffuse anaplasia in Wilms tumor—new definitions with prognostic significance: a report from the National Wilms Tumor Study Group. Am J Surg Pathol 20:909–920PubMedCrossRef

12.

Fukuzawa R, Heathcott RW, Sano M, Morison IM, Yun K, Reeve AE (2004) Myogenesis in Wilms’ tumors is associated with mutations of the WT1 gene and activation of Bcl-2 and the Wnt signaling pathway. Pediatr Dev Pathol 7:125–137CrossRefPubMed

13.

Gerald WL, Gramling TS, Sens DA, Garvin AJ (1992) Expression of the 11p13 Wilms’ tumor gene, WT1, correlates with histologic category of Wilms’ tumor. Am J Pathol 140:1031–1037PubMed

14.

Grundy P, Coopes M (1996) An overview of the clinical and molecular genetics of Wilms’ tumor. Med Pediatr Oncol 27:394–397CrossRefPubMed

15.

Guertl B, Ratschek M, Harms D, Jaenig U, Leuschner I, Poremba C, Hoefler G (2003) Clonality and loss of heterozygosity of WT genes are early events in the pathogenesis of nephroblastomas. Hum Pathol 34:278–281CrossRefPubMed

16.

Karnik P, Chen P, Paris M, Yeger H, Williams BR (1998) Loss of heterozygosity at chromosome 11p15 in Wilms tumors: identification of two independent regions. Oncogene 7:237–240CrossRef

17.

Kopp P, Jaggi R, Tobler A, Borisch B, Oestreicher M, Sabacan L, Jameson JL, Fey MF (1997) Clonal X-inactivation analysis of human tumours using the human androgen receptor gene (HUMARA) polymorphism: a non-radioactive and semiquantitative strategy applicable to fresh and archival tissue. Mol Cell Probes 11:217–228CrossRefPubMed

18.

Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Houseman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691CrossRefPubMed

19.

Li Cm, Kim CE, Margolin AA, Guo M, Zhu J, Mason JM, Hensle TW, Murty VV, Grundy PE, Fearon ER, D´Agati V, Licht JD, Tycko B (2004) CTNNB1 mutations and overexpression of Wnt/beta-catenin target genes in WT1-mutant Wilms tumors. Am J Pathol 165:1943–1953PubMed

20.

Lyon MF (1961) Gene action in the X-chromosome of the mouse. Nature 190:372–373PubMedCrossRef

21.

Mierau GW, Beckwith JB, Weeks DA (1987) Ultrastructure and histogenesis of the renal tumors of childhood: an overview. Ultrastruct Pathol 11:313–333PubMedCrossRef

22.

Miwa H, Tomlinson GF, Timmons CF, Huff V, Cohn SL, Strong LC, Saunders GF (1992) RNA expression of the WT1 gene in Wilms’ tumors in relation to histology. J Natl Cancer Inst 84:181–187PubMedCrossRef

23.

Murphy WM, Beckwith JB, Farrow GM (1994) Tumors of the kidney, bladder, and related urinary structures. In: Atlas of tumor pathology, 3rd series, fascicle 11. Armed Forces Institute of Pathology, Washington, pp 12–54

24.

Ramburan A, Oladiran F, Smith C, Hadley GP, Govender D (2005) Microsatellite analysis of the adenomatous polyposis coli (APC) gene and immunoexpression of beta catenin in nephroblastoma: a study including 83 cases treated with preoperative chemotherapy. J Clin Pathol 58:44–50CrossRefPubMed

25.

Schumacher V, Schneider S, Figge A, Wildhardt G, Harms D, Schmidt D, Weirich A, Ludwig R, Roya-Pokora B (1997) Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology. Proc Natl Acad Sci USA 94:3972–3977CrossRefPubMed

26.

Wilimas JA, Dow LW, Douglass EC, Jenkins JJIII, Jacobson RJ, Moohr J, Fialkow PJ (1991) Evidence for clonal development of Wilms’ tumor. Am J Pediatr Hematol Oncol 13:26–28PubMedCrossRef

Title: Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes
Authors: Barbara Guertl
Ivo Leuschner
Dieter Harms
Gerald Hoefler
Publication date: 01-08-2006
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 2/2006
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-006-0225-2

At a glance: The STEP trials

Springer Medicine

Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2006

A murine model of NKT cell-mediated liver injury induced by alpha-galactosylceramide/d-galactosamine

Immunohistochemical evaluation of a novel clone of monoclonal anti-MYCN antibody B8.4B in neuroblastic tumours: a correlation with MYCN gene status

Coexistence of Epstein–Barr virus-associated gastric carcinoma with malignant lymphoma: report of two cases

The cardiac isoform of α-actin in regenerating and atrophic skeletal muscle, myopathies and rhabdomyomatous tumors: an immunohistochemical study using monoclonal antibodies

Nonhypotensive dose of β-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure

Preinvasive intraductal neoplasia in salivary adenocarcinoma, not otherwise specified