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Decreased CDKN1C Expression in Congenital Alveolar Rhabdomyosarcoma Associated with Beckwith-Wiedemann Syndrome

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Abstract

The Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by somatic overgrowth and predisposition to embryonal tumors, such as Wilm’s tumor, hepatoblastoma, neuroblastoma and rhabdomyosarcoma (RMS). BWS is associated with various genetic alterations: a variety of molecular lesions are described on the chromosome 11p15, affecting gene expression for IGF2, H19, CDKN1C and KCNQ1OT1. Alveolar RMS also recognises characteristic genetic alterations: two types of translocations, t(2,13) or t(1,13), that generate the PAX3-FKHR or PAX7-FKHR fusion proteins. It has been postulated however, that in BWS this kind of tumor occurs without this characteristic chromosomal rearrangement. The authors describe case of a neonate with BWS that presented at birth with cutaneous metastasis due to alveolar RMS. Genetic analysis showed lack of the two characteristic translocations in the tumor tissue, supporting a different oncogenic pathway of alveolar RMS in children with BWS.

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References

  1. Abi Habib W, Azzi S, Bioude F, et al. Extensive investigation of the IGF2/H19 imprinting control region reveals novel OCT4/SOX2 binding site defects associated with specific methylation patterns in Beckwith-Wiedemann syndrome. Hum Mol Genet. 2014;23:5763–73.

    Article  PubMed  Google Scholar 

  2. Romanelli V, Belinchon A, Benito-Sanz S, et al. CDKN1C (p57Kip2) analysis in Beckwith-Wiedemann syndrome (BWS) patients: genotype-phenotype correlations, novel mutations and polymorphisms. Am J Med Genet Part A. 2010;152A:1390–7.

    CAS  PubMed  Google Scholar 

  3. Weksberg R, Nishikawa J, Caluseriu O, et al. Tumor development in Beckwith-Wiedemann syndrome is associated with a variety of constitutional molecular 11p15 alterations including imprinting defects of KCNQ1OT1. Hum Mol Genet. 2001;10:2989–3000.

    Article  CAS  PubMed  Google Scholar 

  4. Pappas JG. The clinical course of an overgrowth syndrome, from diagnosis in infancy through adulthood: the case of Beckwith-Wiedemann syndrome. Curr Probl Pediatr Adolesc Health Care. 2015;45:112–7.

    Article  PubMed  Google Scholar 

  5. DeBaun MR, Tucker MA. Risk of cancer during the first four years of life in children from the Beckwith-Wiedemann syndrome registry. J Pediatr. 1998;132:398–400.

    Article  CAS  PubMed  Google Scholar 

  6. Kuroiwa M, Sakamoto J, Shimada A, et al. Manifestation of alveolar rhabdomyosarcoma as primary cutaneous lesions in a neonate with Beckwith-Wiedemann syndrome. J Pediatr Surg. 2009;44:e31–5.

    Article  PubMed  Google Scholar 

  7. Rodriguez-Galindo C, Hill DA, Onyekwere O, et al. Neonatal alveolar rhabdomyosarcoma with skin and brain metastases. Cancer. 2001;92:1613–20.

    Article  CAS  PubMed  Google Scholar 

  8. Hayashi K, Ohtsuki Y, Takahashi K, et al. Congenital alveolar rhabdomyosarcoma with multiple skin metastases. Report of a case. Acta Pathol Jpn. 1988;38:241–8.

    CAS  PubMed  Google Scholar 

  9. Mondì V, Piersigilli F, Salvatori G, Auriti C. The skin as an early expression of malignancies in the neonatal age: a review of the literature and a case series. Biomed Res Int. 2015;2015:809406.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Smith AC, Squire JA, Thorner P, et al. Association of alveolar rhabdomyosarcoma with the Beckwtih-Wiedemann syndrome. Pediatr Dev Pathol. 2001;4:550–8.

    Article  CAS  PubMed  Google Scholar 

  11. Pettinati MJ, Haines JL, Higgins RR, Wappner RS, Palmer CG, Weaver DD. Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature. Hum Genet. 1986;74:143–54.

    Article  Google Scholar 

  12. Weksberg R, Shen DR, Fei YL, Song QL, Squire J. Disruption of insulin like growth factor 2 imprinting in Beckwith-Wiedemann syndrome. Nat Genet. 1993;5:143–50.

    Article  CAS  PubMed  Google Scholar 

  13. Diaz-Meyer N, Day CD, Khatod K, et al. Silencing of CDKN1C (p57KIP2) is associated with hypomethylation at KvDMR1 in Beckwith-Wiedemann syndrome. J Med Genet. 2003;40:797–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pateras IS, Apostolopoulou K, Niforou K, Kotsinas A, Gorgoulis VG. p57KIP2: “Kipping” the cell under control. Mol Cancer Res. 2009;7:1902–19.

    Article  CAS  PubMed  Google Scholar 

  15. Shuman C, Becwith JB, Smith AC, Wekseberg R. Beckwith-Wiedemann syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.

  16. Lobe E, Wiener ES, Hays DM, et al. Neonatal rhabdomyosarcoma: the IRS experience. J Pediatr Surg. 1994;29:1167–70.

    Article  CAS  PubMed  Google Scholar 

  17. Dillon PW, Whalen TV, Azizkhan RG, et al. Neonatal soft tissue sarcomas: the influence of pathology on treatment and survival. Children’s cancer group surgical committee. J Pediatr Surg. 1995;30:1038–41.

    Article  CAS  PubMed  Google Scholar 

  18. Ferrari A, Orbach D, Sultan I, et al. Neonatal soft tissue sarcomas. Semin Fetal Neonatal Med. 2012;17:231–8.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medical and Surgical Neonatology, Bambino Gesù Children’s Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy

    Fiammetta Piersigilli, Cinzia Auriti, Vito Mondì, Guglielmo Salvatori & Olivier Danhaive

  2. Department of Pathology, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy

    Paola Francalanci

  3. Department of Pediatrics, University of California, Benioff Children’s Hospital, San Francisco, CA, USA

    Olivier Danhaive

Authors
  1. Fiammetta Piersigilli
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  2. Cinzia Auriti
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  3. Vito Mondì
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  4. Paola Francalanci
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  5. Guglielmo Salvatori
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  6. Olivier Danhaive
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Corresponding author

Correspondence to Vito Mondì.

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FP, VM, GS: Wrote the manuscript; OD and PF: Contribuited to molecular genetic testing for BWS; PF: Involved in bioptical analysis; FP, CA, GS, VM, OD: Involved in management of case; OD and CA: Provided critical comments. OD will act as guarantor for the paper.

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Piersigilli, F., Auriti, C., Mondì, V. et al. Decreased CDKN1C Expression in Congenital Alveolar Rhabdomyosarcoma Associated with Beckwith-Wiedemann Syndrome. Indian J Pediatr 83, 1476–1478 (2016). https://doi.org/10.1007/s12098-016-2187-y

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  • DOI: https://doi.org/10.1007/s12098-016-2187-y

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