Anne Crucis1, Wilfrid Richer2,3, Laurence Brugières4, Christophe Bergeron5, Aude Marie-Cardine6, Jean-Louis Stephan7,8, Pauline Girard9, Nadege Corradini10, Martine Munzer11, Brigitte Lacour12, Veronique Minard-Colin4, Sabine Sarnacki13,14, Dominique Ranchere-Vince15, Daniel Orbach2, Franck Bourdeaut2,3,16. 1. Hopital Necker Enfants-Malades, Service de Reanimation pédiatrique, Paris, France. 2. INSERMU830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France. 3. SIRIC, Recherche Translationnelle en Oncologie Pediatrique, Institut Curie, Paris, France. 4. Département d'Oncologie de l'Enfant et l'Adolescent, Institut Gustave Roussy, Villejuif, France. 5. Institut d'hemato-oncologiePediatrique, Centre Léon Berard, Lyon, France. 6. CHU de Rouen,, Service d'hémato-oncologie pédiatrique, Rouen, France. 7. CHU de Saint-Etienne, Service d'hémato-oncologie pédiatrique, Saint-Etienne, France. 8. Universite Saint-Etienne, Saint-Etienne, France. 9. CHU de Grenoble, Service d'hémato-oncologie pédiatrique, Grenoble, France. 10. CHU d'Amiens, Service d'hémato-oncologie pédiatrique, Amiens, France. 11. CHU de Nantes, Service d'hémato-oncologie pédiatrique, Nantes, France. 12. Registre national des tumeurs solides de l'enfant, CESP INSERM, Vandoeuvre-les-Nancy, France. 13. Université Paris Rene Descartes, Paris, France. 14. Hopital Necker Enfants-Malades, Service de chirurgie infantile, Paris, France. 15. Centre Leon Berard, Service d'anatomie Pathologique, Lyon, France. 16. Institut Curie, Departement d'oncologie pédiatrique adolescent jeune adulte, Paris, France.
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.
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-NF1patients. 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.
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