Clinical Trial: Analysis of Peripheral Nerve Sheath Tumors (PNSTs) in Neurofibromatosis Type 1 (NF1) Patients
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Observational
Official Title: Analysis of Peripheral Nerve Sheath Tumors in Neurofibromatosis Type 1 Patients
Brief Summary:
Neurofibromatosis type 1 (NF1) is a frequent, autosomal dominant disorder caused by heterozygous mutations (intragenic or microdeletion) of the NF1 tumor suppressor gene (chr.17q11.2). One of the clinical features is the development of benign and malignant tumors. The most common benign tumors in these patients are tumors of the peripheral nerve sheath, named neurofibromas (cutaneous, subcutaneous and plexiform). Every NF1 patient has a life time risk of 8 to 13% of developing a malignant peripheral nerve sheath tumor (MPNST) out of a pre-existing neurofibroma. In patients with a NF1 microdeletion (5% of NF1 patients), this risk is even twice as high compared to patients with an intragenic mutation. MPNSTs lead to a bad prognosis for the patient, with an overall five-year survival of less than 25%. To know more about the development and progression of these tumors, they will be screened by microarray comparative genome hybridization (Leuven) and full exome sequencing (Leuven). Further experiments will be done in cooperation (bidirectional) with the foreign labs of Victor Mautner (Germany), André Bernards (USA), Karen Cichowski (USA) and Yuan Zhu (USA).
For all these experiments, we will make use of tumoral rest material removed from NF1 patients.
Detailed Summary:
Introduction Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder occuring in 1 out of 3500 living newborns. The disease is caused by heterozygous mutations of the NF1 gene, located on chromosome 17q11.2. The NF1 gene encodes the tumor suppressor neurofibromin, a negative regulator of the RAS/MAPK pathway. In approximately 95% of patients, the heterozygous mutation is intragenic. The remaining 5% of patients are carrier of a microdeletion, mostly the type 1 deletion, in which apart from the NF1 gene, 14 additional protein coding genes are located.
Clinically, NF1 patients have café-au-lait maculae, freckling, Lisch nodules and neurofibromas. Also cognitive problems, bone lesions and optic pathway gliomas are common in these patients.
Neurofibromas are benign neoplasms of the peripheral nerve sheath, which appear everywhere on the body of almost every NF1 patient. Neurofibromas are composed of different cell types like Schwann cells, fibroblasts, mast cells and perineurial cells. If in Schwann cells of NF1 patients the wild-type NF1 allele is inactivated in a heterozygous microenvironment, a neurofibroma will be formed. There are 3 types of neurofibromas: cutaneous, subcutaneous and plexiform. Cutaneous and subcutaneous neurofibromas appear during adolescence as isolated nodules in or under the skin, respectively. Plexiform neurofibromas are congenital and can spread along a large segment of a peripheral nerve. NF1 microdeletion patients have in general more neurofibromas and they appear at a younger age.
Every NF1 patient has a life time risk of 8 to 13% to develop a malignant peripheral nerve sheath tumor (MPNST) out of a pre-existing (plexiform) neurofibroma. This risk is even twice as high for NF1 microdeletion patients compared to patients with an intra
Sponsor: Katholieke Universiteit Leuven
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Katholieke Universiteit Leuven
Dates:
Date Received: October 8, 2010
Date Started: September 2007
Date Completion: December 2010
Last Updated: October 8, 2010
Last Verified: October 2010
