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Methylation Statuses of H19DMR and KvDMR at WT2 in Wilms Tumors in Taiwan

  • Original Article
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Pathology & Oncology Research

Abstract

Wilms tumor is the most common pediatric renal malignancy. Several genetic loci have been shown to be associated with its formation. Genetic or epigenetic aberrations at WT1 and WT2 loci have been implicated in the etiology of the majority of sporadic Wilms tumors. In our previous study, most Wilms tumors tested negative for both constitutional mutations and somatic mutations in the WT1 gene. Thus, WT2 may play an important role in these tumors. In the present study, we analyzed the methylation statuses of WT2 at 11p15 using methylation sensitive multiplex ligation-dependent probe amplification in six Wilms tumors. Paternal uniparental disomy at WT2 was observed in two Wilms tumors with epithelial components due to hypermethylation at H19DMR and hypomethylation at KvDMR. Our findings highlight the benefits of testing for 11p15 epigenetic abnormalities to identify Wilms tumors with epithelial components.

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Abbreviations

DMR:

differentially methylated region

DNA:

deoxyribonucleic acid

IC:

imprinting center

MAPK:

mitogen-activated protein kinase

MS-MLPA:

methylation sensitive multiplex ligation-dependent probe amplification

UV-VIS:

ultraviolet–visible

References

  1. Brown KW, Malik KT (2001) The molecular biology of Wilms tumour. Expert Rev Mol Med 2001:1–16

    Article  CAS  Google Scholar 

  2. Pastore G, Znaor A, Spreafico F, Graf N, Pritchard-Jones K, Steliarova-Foucher E (2006) Malignant renal tumours incidence and survival in European children (1978-1997): report from the automated childhood Cancer information system project. Eur J Cancer 42:2103–2114

    Article  Google Scholar 

  3. Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F et al (2017) International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol 18:719–731

    Article  Google Scholar 

  4. Treger TD, Chowdhury T, Pritchard-Jones K, Behjati S et al (2019) The genetic changes of Wilms tumour. Nat Rev Nephrol 15:240–251

    Article  Google Scholar 

  5. PDQ Pediatric Treatment Editorial Board (2002) Wilms Tumor and Other Childhood Kidney Tumors Treatment (PDQ®): Health Professional Version. PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US) 2002–2020

  6. Gadd S, Huff V, Walz AL, Ooms A, Armstrong AE, Gerhard DS et al (2017) A Children's oncology group and TARGET initiative exploring the genetic landscape of Wilms tumor. Nat Genet 49:1487–1494

    Article  CAS  Google Scholar 

  7. Mahamdallie S, Yost S, Poyastro-Pearson E, Holt E, Zachariou A, Seal S et al (2019) Identification of new Wilms tumour predisposition genes: an exome sequencing study. Lancet Child Adolesc Health 3:322–331

    Article  Google Scholar 

  8. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60:509–520

    Article  CAS  Google Scholar 

  9. 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 17:237–240

    Article  CAS  Google Scholar 

  10. Al-Hussain T, Ali A, Akhtar M (2014) Wilms tumor: an update. Adv Anat Pathol 21:166–173

    Article  Google Scholar 

  11. Cardoso LC, Tenorio Castano JA, Pereira HS, Lima MA, Dos Santos AC, de Faria PS et al (2012) Constitutional and somatic methylation status of DMRH19 and KvDMR in Wilms tumor patients. Genet Mol Biol 35:714–724

    Article  CAS  Google Scholar 

  12. Dekel B, Metsuyanim S, Schmidt-Ott KM, Fridman E, Jacob-Hirsch J, Simon A et al (2006) Multiple imprinted and stemness genes provide a link between normal and tumor progenitor cells of the developing human kidney. Cancer Res 66:6040–6049

    Article  CAS  Google Scholar 

  13. Scott RH, Douglas J, Baskcomb L, Huxter N, Barker K, Hanks S et al (2008) Constitutional 11p15 abnormalities, including heritable imprinting center mutations, cause nonsyndromic Wilms tumor. Nat Genet 40:1329–1334

    Article  CAS  Google Scholar 

  14. Lu MY, Wang WC, Lin CW, Chang A, Lai YC (2014) Identification of a constitutional mutation in the WT1 gene in Taiwanese patients with Wilms tumor. Adv Biosci Biotechnol 5:230–234

    Article  Google Scholar 

  15. Chiang MR, Kuo CW, Wang WC, Hou TC, Kuo CY, Lu MY et al (2019) Correlations between histological and array comparative genomic hybridization characterizations of Wilms tumor. Pathol Oncol Res 25:1199–1206

    Article  CAS  Google Scholar 

  16. Wang WC, Lai YC (2016) Genetic analysis results of mature cystic teratomas of the ovary in Taiwan disagree with the previous origin theory of this tumor. Hum Pathol 52:128–135

    Article  Google Scholar 

  17. Dao D, Walsh CP, Yuan L, Gorelov D, Feng L, Hensle T et al (1999) Multipoint analysis of human chromosome 11p15/mouse distal chromosome 7: inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19 silencing in Wilms' tumorigenesis and methylation hyper-dependence of H19 imprinting. Hum Mol Genet 8:1337–1352

    Article  CAS  Google Scholar 

  18. Mancini-DiNardo D, Steele SJ, Ingram RS, Tilghman SM (2003) A differentially methylated region within the gene Kcnq1 functions as an imprinted promoter and silencer. Hum Mol Genet 12:283–294

    Article  CAS  Google Scholar 

  19. Hubertus J, Lacher M, Rottenkolber M, Müller-Höcker J, Berger M, Stehr M et al (2011) Altered expression of imprinted genes in Wilms tumors. Oncol Rep 25:817–823

    Article  CAS  Google Scholar 

  20. Scott RH, Murray A, Baskcomb L, Turnbull C, Loveday C, Al-Saadi R et al (2012) Stratification of Wilms tumor by genetic and epigenetic analysis. Oncotarget 3:327–335

    Article  Google Scholar 

  21. Verschuur AC, Vujanic GM, Van Tinteren H, Jones KP, de Kraker J, Sandstedt B (2010) Stromal and epithelial predominant Wilms tumours have an excellent outcome: the SIOP 93 01 experience. Pediatr Blood Cancer 55:233–238

    Article  Google Scholar 

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Acknowledgments

The authors would like to thank GenePhile Bioscience Laboratory of Ko’s Obstetrics and Gynecology Clinic for help with acquisition of data.

Funding

This work was supported by a grant from Chung Shan Medical University (grant number CSMU-INT-108-2). The funding body had no role in the study design, study setting, analysis, or writing of the manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

    Meng-Yao Lu

  2. Department of Obstetrics and Gynecology, Jen-Ai Hospital, Taichung, Taiwan

    Wen-Chung Wang

  3. Department of Pathology, Jen-Ai Hospital, Taichung, Taiwan

    Tai-Cheng Hou & Chen-Yun Kuo

  4. Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, No.110, Sec. 1, Chien Kuo N. Road, Taichung, 402, Taiwan

    Yen-Chein Lai

  5. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

    Yen-Chein Lai

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  1. Meng-Yao Lu
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  2. Wen-Chung Wang
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  4. Chen-Yun Kuo
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  5. Yen-Chein Lai
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Correspondence to Yen-Chein Lai.

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The authors have consulted the journal policy regarding compliance with ethical standards and declare that accepted principles of ethical and professional conduct have been followed. The authors include information regarding sources of funding (previous section) and potential conflicts of interest (financial or non-financial) (next section). As no patients were involved and no personal information was used, informed consent was not applicable.

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The authors declare that they have no competing interests.

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Ethics approval of the study procedures was obtained from the Institutional Review Board of Chung Shan Medical University Hospital via reference number CS2–16003.

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Lu, MY., Wang, WC., Hou, TC. et al. Methylation Statuses of H19DMR and KvDMR at WT2 in Wilms Tumors in Taiwan. Pathol. Oncol. Res. 26, 2153–2159 (2020). https://doi.org/10.1007/s12253-020-00802-6

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  • DOI: https://doi.org/10.1007/s12253-020-00802-6

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