Tumor Spectrum in Children With Noonan Syndrome and SOS1 or RAF1 Mutations

Denayer E., Devriendt K., de Ravel T., Van Buggenhout G., Smeets E., Francois I., ...More

GENES CHROMOSOMES & CANCER, vol.49, no.3, pp.242-252, 2010 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 49 Issue: 3
  • Publication Date: 2010
  • Doi Number: 10.1002/gcc.20735
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.242-252


Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in PTPN11, KRAS, SOS1, and RAF1 We performed SOS1, RAF1, BRAF MEK1, and MEK2 mutation analysis in a cohort of 102 PTPN11- and KRAS-negative NS patients and found pathogenic SOS1 mutations in 10, RAF1 mutations in 4, and BRAF mutations in 2 patients. Three novel SOS1 mutations were found. One was classified as a rare benign variant and the other remains unclassified. We confirm a high prevalence of pulmonic stenosis and ectodermal abnormalities in SOS1-positive patients. Three patients with SOS1 mutations presented with tumors (embryonal rhabdomyosarcoma, Sertoli cell testis tumor, and granular cell tumors of the skin). One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in ISIS patients with germ line SOS1 mutations. (C) 2009 Wiley-Liss, Inc.