Clinical Trial: Microarray CGH Analysis of Circulating Tumoral Plasma DNA in NF1 Patients With MPNSTs
Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Observational
Official Title: Analysis of Circulating Tumor DNA in Plasma of Neurofibromatosis Type 1 Patients With MPNSTs Using Microarray CGH
Brief Summary: Neurofibromatosis type 1 (NF1) is a frequent autosomal dominant disorder, caused by heterozygous mutations of the NF1 tumor suppressor gene (chr.17q11.2). One of the main clinical features is the development of benign and malignant tumors. The most common benign tumors in these patients are tumors of the peripheral nerve, named neurofibromas. Every NF1 patient has a life time risk of 8-13% to develop a malignant peripheral nerve sheath tumor (MPNST) starting from a pre-existing neurofibroma. MPNSTs lead to a bad prognosis for the patient, with an overall five-year survival of less than 25%. Complete resection is the standard treatment, but this is often difficult due to the size of the tumors and the location on important nerves, moreover the tumor is frequently metastatic at the time of diagnosis. For MPNSTs, like for other cancers, the extent and the spread of the disease at time of diagnosis is an important factor in determining treatment outcome. In this regard, the analysis of tumor derived cell-free circulating DNA in plasma of NF1 patients would open up the possibility to diagnose and monitor the development and progression of MPNSTs using a small blood sample. In cooperation with P. Schöffski (UZLeuven), we plan to collect blood samples from cancer patients to optimize the DNA extraction procedure starting from plasma samples. It is known that patients with cancer have a higher amount of free circulating DNA in plasma than individuals without cancer and therefore we want to optimize the DNA extraction procedure on plasma from patients with cancer. In the meantime, matching MPNST and plasma samples from NF1 patients will be collected and sent to us from the University of Eppendorf (Victor Mautner) to optimize the array CGH protocol for the detection of copy number changes in plasma DNA of NF1 patients with MPNSTs.
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 oncogene. Clinically, NF1 patients have café-au-lait maculae, freckling, Lisch nodules and neurofibromas. Cognitive problems, bone lesions and optic pathway gliomas are also common in these patients.
Neurofibromas are benign neoplasms of the peripheral nerve sheath, which can appear anywhere in the body of NF1 patients. 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, a neurofibroma will be formed. There are 3 types of neurofibromas: cutaneous, subcutaneous and plexiform. Cutaneous 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. Subcutaneous neurofibromas are discrete nodules located on peripheral nerves and the timing of their origin is not known, but they are probably also prenatal in origin.
Every NF1 patient has a life time risk of 8 to 13% to develop a malignant peripheral nerve sheath tumor (MPNST). This risk is even twice as high for a subpopulation of NF1 patients, namely patients with an NF1 microdeletion. MPNSTs are difficult to diagnose in early phase because of the large number of tumors and diverse locations often seen in these patients. These tumors infiltrate easily in surrounding tissue and frequently give rise to metastases. At this moment, the only available treatment is surgical removal of these MPNSTs. Complete
Sponsor: Katholieke Universiteit Leuven
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Information By: Katholieke Universiteit Leuven
Dates:
Date Received: October 8, 2010
Date Started: October 2010
Date Completion: December 2011
Last Updated: October 8, 2010
Last Verified: October 2010
