NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies

Giovanni Ponti, Davide Martorana, Giovanni Pellacani, Cristel Ruini, Pietro Loschi, Alessio Baccarani, Giorgio De Santis, Annamaria Pollio, Tauro Maria Neri, Victor Desmond Mandel, Antonio Maiorana, Livia Maccio, Monia Maccaferri, Aldo Tomasi

Research output: Contribution to journalArticlepeer-review


Background/Aim: Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Patients and Methods: Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Results: Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. Conclusion: This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1.

Original languageEnglish
Pages (from-to)3021-3030
Number of pages10
JournalAnticancer Research
Issue number6
Publication statusPublished - Jun 1 2014


  • Elephantiasis neuromatosa; GIST; malignant peripheral nerve sheet tumors
  • Neurofibromatosis type 1
  • Plexiform neurofibroma; NF1 truncating mutations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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