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Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations
Author(s) -
Denayer Ellen,
Devriendt Koen,
de Ravel Thomy,
Van Buggenhout Griet,
Smeets Eric,
Francois Inge,
Sznajer Yves,
Craen Margarita,
Leventopoulos George,
Mutesa Léon,
Vandecasseye Willy,
Massa Guy,
Kayserili Hulya,
Sciot Raf,
Fryns JeanPierre,
Legius Eric
Publication year - 2010
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20735
Subject(s) - noonan syndrome , costello syndrome , mutation , medicine , genetics , biology , gene , kras
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 NS patients with germ line SOS1 mutations. © 2009 Wiley‐Liss, Inc.