Molecular Studies of Candidate Gene Somatic Mutations in Human Schwannoma Tumors


  • Amanda Victoria Martinez University of Florida



Schwannomas are benign Schwann cell tumors on the peripheral nerves that occur in the autosomal dominant conditions of NF2 (neurofibromatosis type 2) or schwannomatosis. NF2 is caused by germline mutations in the NF2 gene, and patients can form tumors when the remaining normal gene copy is mutated. In schwannomatosis, two genes are known to have germline mutations: SMARCB1 and LZTR1, both near the NF2 gene on chromosome 22. Schwannomas in schwannomatosis have variable somatic deletions of multiple genes, and the tumors also have a risk of becoming malignant. These tumors can cause deformities, functional problems, substantial pain, and even lead to death. Schwannomas are difficult to treat because surgery involves cutting the affected nerves. There are currently no drug therapies, and due to the paucity of cell cultures and cell lines, there is a lack of molecular and cell biology data about schwannomas. The goal of this work was to better characterize a set of 20 tumors, to contribute information helpful in developing more targeted therapies. This involved loss of heterozygosity study using polymorphisms in or near the genes NF2, LZTR1 and SMARCB1 to identify somatic deletions. DNA sequencing of SMARCB1 exons was also carried out to search for germline and somatic mutations. This work revealed several mutations that contribute new knowledge to the field.