Malignant Melanoma and Wiedemann-Beckwith Syndrome in Childhood

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
• 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
• 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
• 4 Downard CD, Rapkin LB, Gow KW. Melanoma in children and adolescents.  Surg Oncol. 2007;  16 215-220
• 5 Elliott M, Maher ER. Beckwith-Wiedemann syndrome.  J Med Genet. 1994;  31 560-564
• 6 Engel JR, Smallwood A, Harper A. et al . Epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome.  J Med Genet. 2000;  37 921-926
• 7 Frühwald MC, Witt O. The epigenetics of cancer in children.  Klin Pädiatr. 2008;  220 333-341
• 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
• 9 Hamre MR, Chuba P, Bakhshi S. et al . Cutaneous melanoma in childhood and adolescence.  Pediatr Hematol Oncol. 2002;  19 309-317
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 19 Wiedemann HR. Familial malformation complex with umbilical hernia and macroglossia – a “new syndrome”?.  J Genet Hum. 1964;  13 223-232
• 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
• 21 Yu L, Xu H, Wasco MJ. et al . IMP-3 expression in melanocytic lesions.  J Cutan Pathol. 2010;  37 316-322

Correspondence