Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma

Marjolijn C J Jongmans, Peter M Hoogerbrugge, Linda Hilkens, Uta Flucke, Ineke van der Burgt, Kees Noordam, Martina Ruiterkamp-Versteeg, Helger G Yntema, Willy M Nillesen, Marjolijn J L Ligtenberg, Ad Geurts van Kessel, Roland P Kuiper, Nicoline Hoogerbrugge

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

32 Citaten (Scopus)


Noonan Syndrome (NS) is an autosomal dominant condition characterized by short stature, facial dysmorphisms, and congenital heart defects, and is caused by mutations in either PTPN11, KRAS, NRAS, SHOC2, RAF1, or SOS1. Furthermore, NS is known for its predisposition to develop cancer, particularly hematological malignancies and specific solid tumors, mainly neuroblastoma and embryonal rhabdomyosacroma (ERMS). Until recently, however, cancer predisposition in NS patients with SOS1 mutations was not reported. Here we present a NS patient with a de novo germline SOS1 mutation (p.Lys728Ile) and ERMS. This heterozygous germline mutation was homozygously present in the ERMS of this patient due to an acquired uniparental disomy (UPD) of chromosome 2. In addition, several other chromosomal aberrations were encountered, some of which are known to recurrently occur in ERMS. Sequence analysis of the SOS1 gene in 20 sporadic ERMS tumors failed to reveal any pathogenic mutations, implicating that SOS1 is not a major player in the development of this tumor outside the context of NS.

Originele taal-2Engels
Pagina's (van-tot)635-41
Aantal pagina's7
TijdschriftGenes Chromosomes and Cancer
Nummer van het tijdschrift7
StatusGepubliceerd - jul. 2010
Extern gepubliceerdJa


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