Brain tumor
Glioblastoma multiforme (GBM) is the most aggressive (grade IV) and most common form of a malignant brain tumor. Even when aggressive multimodality therapy consisting of radiotherapy, chemotherapy, and surgical excision is used, median survival is only 12–17 months. Standard therapy for glioblastoma multiforme consists of maximal surgical resection of the tumor, followed by radiotherapy between two and four weeks after the surgical procedure to remove the cancer, then by chemotherapy, such as temozolomide. Most patients with glioblastoma take a corticosteroid, typically dexamethasone, during their illness to relieve symptoms. Experimental treatments include targeted therapy, gamma knife radiosurgery, boron neutron capture therapy and gene therapy.
Genome instability
Cancers usually result from disruption of a tumor repressor or dysregulation of an oncogene. Knowing that B-cells experience DNA breaks through development can give insight to the genome of lymphomas. Many types of lymphoma are caused by chromosomal translocation, which can arise from breaks in DNA leading to incorrect joining. In Burkitt’s lymphoma, c-myc, an oncogene encoding a transcription factor, is translocated after the promoter of the immunoglobulin gene, leading dysregulation of c-myc transcription. Since immunoglobulins are essential to a lymphocyte and highly expressed to increase detection of antigens, c-myc is then also highly expressed leading to transcription of its targets which are involved in cell proliferation. Mantle cell lymphoma is characterized by fusion of cyclin D1 to the immunoglobulin locus. Cyclin D1 inhibits Rb, a tumor suppressor, leading to tumorigenesis. Follicular lymphoma results from the translocation of immunoglobulin promoter to the Bcl-2 gene, giving rise to large amounts of Bcl-2 protein which inhibits apoptosis. DNA-damaged B-cells no longer undergo apoptosis leading to further mutations which could affect driver genes leading to tumorigenesis. The location of translocation in the oncogene shares structural properties of the target regions of AID, suggesting that the oncogene was a potential target of AID, leading to a double-stranded break that was translocated to the immunoglobulin gene locus through NHEJ repair.