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Klin Padiatr 2010; 222(6): 388-390
DOI: 10.1055/s-0030-1267152
Case Report

© Georg Thieme Verlag KG Stuttgart · New York

Malignant Melanoma and Wiedemann-Beckwith Syndrome in Childhood

Malignes Melanom und Wiedemann-Beckwith-Syndrom im KindesalterE. Livingstone1 , A. Caliebe2 , F. Egberts3 , E. Proksch3 , K. Buiting4 , C. Schubert†5 , A. Claviez6 , R. Siebert2 , A. Hauschild3
  • 1Department of Dermatology, University Hospital Duisburg-Essen, Essen, Germany
  • 2Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Germany
  • 3Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
  • 4Institute of Human Genetics, University Hospital Duisburg-Essen, Essen, Germany
  • 5Institute of Dermatology, Dermatohistopathology, Buchholz, Germany. The author deceased during preparation of this paper.
  • 6Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Germany
Further Information

Publication History

Publication Date:
05 November 2010 (online)

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Abstract

Patients with Wiedemann-Beckwith syndrome (WBS, MIM 130650), a congenital overgrowth syndrome, have a known increased tumor risk especially for embryonic tumors. WBS belongs to the “imprinting” syndromes caused by overexpression of IGF2 and/or loss of CDKN1C on chromosome 11p15.5. A 13-year-old boy with WBS developed a spitzoid malignant melanoma (Clark level V, Breslow index 4.8 mm) on the right cheek. Genetic analyses of the patient's blood showed hypermethylation at the H19 locus on chromosome 11p. The (epi)genetic changes of the WBS locus might have played a role in the pathogenesis of melanoma development.

Zusammenfassung

Patienten mit Wiedemann-Beckwith-Syndrom (WBS, MIM 130650), einem kongenitalen Hochwuchssyndrom, weisen ein erhöhtes Tumorrisiko speziell für embryonale Tumoren auf. Das WBS gehört zu den sog. „Imprinting”-Syndromen, die durch eine Überexpression von IGF2 und/oder Expressionsverlust von CDKN1C auf Chromosom 11p15.5 charakterisiert sind. Genetische Analysen aus dem Blut eines 13-jährigen Jungen mit WBS und spitzoidem malignem Melanom (Clark Level V, Breslow Index 4,8 mm) zeigten eine Hypermethylierung des H19 Lokus auf Chromosom 11p; dies könnte zur Melanomentstehung beigetragen haben.

Key words

malignant melanoma - Wiedemann-Beckwith syndrome - genomic imprinting - tumor predisposition

Schlüsselwörter

malignes Melanom - Wiedemann-Beckwith-Syndrom - genomisches Imprinting - Tumorprädisposition

References

  • 1 Brecht IB, Graf N, Schweinitz D. et al . Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group.  Klin Pädiatr. 2009;  221 181-185
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Certa U, Seiler M, Padovan E. et al . High density oligonucleotide array analysis of interferon-alpha2a sensitivity and transcriptional response in melanoma cells.  Br J Cancer. 2001;  85 107-114
    CrossrefPubMedGoogle Scholar
  • 3 Certa U, Seiler M, Padovan E. et al . Interferon-a sensitivity in melanoma cells: detection of potential response marker genes.  Recent Results Cancer Res. 2002;  160 85-91
    PubMedGoogle Scholar
  • 4 Downard CD, Rapkin LB, Gow KW. Melanoma in children and adolescents.  Surg Oncol. 2007;  16 215-220
    CrossrefPubMedGoogle Scholar
  • 5 Elliott M, Maher ER. Beckwith-Wiedemann syndrome.  J Med Genet. 1994;  31 560-564
    CrossrefPubMedGoogle Scholar
  • 6 Engel JR, Smallwood A, Harper A. et al . Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome.  J Med Genet. 2000;  37 921-926
    CrossrefPubMedGoogle Scholar
  • 7 Frühwald MC, Witt O. The epigenetics of cancer in children.  Klin Pädiatr. 2008;  220 333-341
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Goldstein AM, Fraser MC, Struewing JP. et al . Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations.  N Engl J Med. 1995;  333 970-974
    CrossrefPubMedGoogle Scholar
  • 9 Hamre MR, Chuba P, Bakhshi S. et al . Cutaneous melanoma in childhood and adolescence.  Pediatr Hematol Oncol. 2002;  19 309-317
    CrossrefPubMedGoogle Scholar
  • 10 Higurashi M, Iijima K, Sugimoto Y. et al . The birth prevalence of malformation syndromes in Tokyo infants: a survey of 14 430 newborn infants.  Am J Med Genet. 1980;  6 189-194
    CrossrefPubMedGoogle Scholar
  • 11 Lam WW, Hatada I, Ohishi S. et al . Analysis of germline CDKN1C (p57KIP2) mutations in familial and sporadic Beckwith-Wiedemann syndrome (BWS) provides a novel genotype-phenotype correlation.  J Med Genet. 1999;  36 518-523
    PubMedGoogle Scholar
  • 12 Lee SK, Kang JS, Jung dJ. et al . Vitamin C suppresses proliferation of the human melanoma cell SK-MEL-2 through the inhibition of cyclooxygenase-2 (COX-2) expression and the modulation of insulin-like growth factor II (IGF-II) production.  J Cell Physiol. 2008;  216 180-188
    CrossrefPubMedGoogle Scholar
  • 13 Pos Z, Wiener Z, Pocza P. et al . Histamine suppresses fibulin-5 and insulin-like growth factor-II receptor expression in melanoma.  Cancer Res. 2008;  68 1997-2005
    CrossrefPubMedGoogle Scholar
  • 14 Pryor JG, Bourne PA, Yang Q. et al . IMP-3 is a novel progression marker in malignant melanoma.  Mod Pathol. 2008;  21 431-437
    CrossrefPubMedGoogle Scholar
  • 15 Rump P, Zeegers MP, van Essen AJ. Tumor risk in Beckwith-Wiedemann syndrome: A review and meta-analysis.  Am J Med Genet A. 2005;  136 95-104
    PubMedGoogle Scholar
  • 16 Schmid-Wendtner MH, Berking C, Baumert J. et al . Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients.  J Am Acad Dermatol. 2002;  46 874-879
    CrossrefPubMedGoogle Scholar
  • 17 Soares MR, Huber J, Rios AF. et al . Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma.  Growth Horm IGF Res. 2010;  20 295-297
    CrossrefPubMedGoogle Scholar
  • 18 Weksberg R, Nishikawa J, Caluseriu O. et al . Tumor development in the 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
    CrossrefPubMedGoogle Scholar
  • 19 Wiedemann HR. Familial malformation complex with umbilical hernia and macroglossia – a “new syndrome”?.  J Genet Hum. 1964;  13 223-232
    PubMedGoogle Scholar
  • 20 Wiedemann HR. Frequency of Wiedemann-Beckwith syndrome in Germany; rate of hemihyperplasia and of tumours in affected children.  Eur J Pediatr. 1997;  156 251
    PubMedGoogle Scholar
  • 21 Yu L, Xu H, Wasco MJ. et al . IMP-3 expression in melanocytic lesions.  J Cutan Pathol. 2010;  37 316-322
    CrossrefPubMedGoogle Scholar

Correspondence

Prof. Dr. Axel Hausschild

Klinik für Dermatologie

Venerologie und Allergologie

Universitätsklinikum

Schleswig-Holstein

Campus Kiel

Schittenhelmstraße 7

24105 Kiel

Phone: +49/431/597 1852

Fax: +49/431/597 1853

Email: ahauschild@dermatology.uni-kiel.de

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