Noonan Syndrome, the SOS1 Gene and Embryonal Rhabdomyosarcoma

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

来源：Genes, Chromosomes and Cancer, 2010, 49(7): 635-641.

DOI：10.1002/gcc.20773

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.Lys72811e) 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.

• 出版日期2010-7