title: Rhabdomyosarcomas in children with neurofibromatosis type I: A national historical cohort.
abstract: BACKGROUND
  Rhabdomyosarcoma (RMS) occasionally occurs in a context of a predisposition syndrome. The most common predisposition syndromes include germline TP53 mutations and constitutive alterations in RAS pathway activation, such as Costello syndrome, Noonan syndrome and neurofibromatosis type 1. We report a national retrospective series of 16 RMS occurring in neurofibromatosis type 1 (NF1) patients during childhood, within a 20-year period.
  
  
  RESULTS
  The mean age at diagnosis of the cancer was 2.5 years. All were embryonal subtype. Most tumours developed in the pelvis. One was metastatic. Chemotherapy and radiotherapy were normally scheduled without any specific toxicity. The 5-year event-free survival and overall survival were 67% and 87%, respectively. Long-term sequel related to chemotherapy consisted in two chronic tubulopathies, hence not obviously different from non-NF1 patients. No second cancer was reported so far with a median follow-up of 9.7 years. The genomic analysis performed on six samples revealed the abnormalities commonly observed in sporadic RMS: gain of chromosome 2 (5/6), 8 (6/6) and chromosome 11p loss of heterozygosity (5/6). Interestingly, we identified small deletions in tumour suppressor genes that may synergize with NF1 inactivation.
  
  
  CONCLUSIONS
  Patients with neurofibromatosis are prone to develop embryonal-type RMS that require the same treatment as sporadic cases.
authors.affiliation: Hopital Necker Enfants-Malades, Service de Reanimation pédiatrique, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Crucis
authors.affiliation: INSERMU830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France.|SIRIC, Recherche Translationnelle en Oncologie Pediatrique, Institut Curie, Paris, France.
authors.forename: Wilfrid
authors.initials: W
authors.lastname: Richer
authors.affiliation: Département d'Oncologie de l'Enfant et l'Adolescent, Institut Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.affiliation: Institut d'hemato-oncologiePediatrique, Centre Léon Berard, Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bergeron
authors.affiliation: CHU de Rouen,, Service d'hémato-oncologie pédiatrique, Rouen, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Marie-Cardine
authors.affiliation: CHU de Saint-Etienne, Service d'hémato-oncologie pédiatrique, Saint-Etienne, France.|Universite Saint-Etienne, Saint-Etienne, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Stephan
authors.affiliation: CHU de Grenoble, Service d'hémato-oncologie pédiatrique, Grenoble, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Girard
authors.affiliation: CHU d'Amiens, Service d'hémato-oncologie pédiatrique, Amiens, France.
authors.forename: Nadege
authors.initials: N
authors.lastname: Corradini
authors.affiliation: CHU de Nantes, Service d'hémato-oncologie pédiatrique, Nantes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.affiliation: Registre national des tumeurs solides de l'enfant, CESP INSERM, Vandoeuvre-les-Nancy, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lacour
authors.affiliation: Département d'Oncologie de l'Enfant et l'Adolescent, Institut Gustave Roussy, Villejuif, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Minard-Colin
authors.affiliation: Université Paris Rene Descartes, Paris, France.|Hopital Necker Enfants-Malades, Service de chirurgie infantile, Paris, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Sarnacki
authors.affiliation: Centre Leon Berard, Service d'anatomie Pathologique, Lyon, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Ranchere-Vince
authors.affiliation: INSERMU830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Orbach
authors.affiliation: INSERMU830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France.|SIRIC, Recherche Translationnelle en Oncologie Pediatrique, Institut Curie, Paris, France.|Institut Curie, Departement d'oncologie pédiatrique adolescent jeune adulte, Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
mesh_terms: D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009456:Neurofibromatosis 1 / Q000150:complications*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000150:complications* / Q000235:genetics / Q000401:mortality
keywords: NF1; neurofibromatosis; predisposition; rhabdomyosarcoma