title: BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours.
abstract: OBJECTIVE
  Benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumours occur either sporadically or are related to neurofibromatosis (NF). The mechanisms involved are well known in NF-related tumours, but still remain unclear in sporadic cases. Somatic BRAF and KRAS mutations represent the most frequent genetic events in melanocytic neoplastic lesions. Because melanocytes and Schwann cells both derive from neural crest cells, we hypothesized that BRAF and KRAS mutations might influence BPNST and MPNST development.
  
  
  RESULTS
  BRAF exon 15 and KRAS exons 2 and 3 polymerase chain reaction (PCR) sequencing was performed in formalin-fixed/paraffin-embedded samples of 99 BPNST and MPNST, related and non-related to NF types 1 and 2. Oncogenic BRAF V600E mutations were found in four of 40 schwannomas (including one acoustic neuroma) and one of 13 MPNST, not associated with NF. A KRAS G12S mutation was also evident in one sporadic schwannoma.
  
  
  CONCLUSIONS
  Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to NF.
authors.affiliation: Department of Oncology, Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Passeig de la Vall d’Hebron 119–129, Barcelona, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Serrano
authors.forename: Sara
authors.initials: S
authors.lastname: Simonetti
authors.forename: Javier
authors.initials: J
authors.lastname: Hernández-Losa
authors.forename: Claudia
authors.initials: C
authors.lastname: Valverde
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrato
authors.forename: Silvia
authors.initials: S
authors.lastname: Bagué
authors.forename: Ruth
authors.initials: R
authors.lastname: Orellana
authors.forename: Rosa
authors.initials: R
authors.lastname: Somoza
authors.forename: Teresa
authors.initials: T
authors.lastname: Moliné
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Pere
authors.initials: P
authors.lastname: Huguet
authors.forename: Cleofé
authors.initials: C
authors.lastname: Romagosa
authors.forename: Santiago
authors.initials: S
authors.lastname: Ramón y Cajal
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins