Noonan syndrome, the SOS1 gene and embryonal rhabdomyosarcoma
Corresponding Author
Marjolijn C. J. Jongmans
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the NetherlandsSearch for more papers by this authorPeter M. Hoogerbrugge
Department of Pediatric Hemato-oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorLinda Hilkens
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorUta Flucke
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorIneke van der Burgt
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorKees Noordam
Department of Pediatric Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMartina Ruiterkamp-Versteeg
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorHelger G. Yntema
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorWilly M. Nillesen
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMarjolijn J. L. Ligtenberg
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorAd Geurts van Kessel
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorRoland P. Kuiper
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorNicoline Hoogerbrugge
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
Marjolijn C. J. Jongmans
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Department of Human Genetics, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the NetherlandsSearch for more papers by this authorPeter M. Hoogerbrugge
Department of Pediatric Hemato-oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorLinda Hilkens
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorUta Flucke
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorIneke van der Burgt
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorKees Noordam
Department of Pediatric Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMartina Ruiterkamp-Versteeg
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorHelger G. Yntema
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorWilly M. Nillesen
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorMarjolijn J. L. Ligtenberg
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorAd Geurts van Kessel
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorRoland P. Kuiper
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorNicoline Hoogerbrugge
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Search for more papers by this authorAbstract
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. © 2010 Wiley-Liss, Inc.
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