Glioblastoma
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive cancer that begins within the brain. Initially, signs and symptoms of glioblastoma are non-specific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Worsening of symptoms often is rapid. This may progress to unconsciousness.
The cause of most cases is unclear. Uncommon risk factors include genetic disorders such as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of brain tumors. They can either start from normal brain cells or develop from an existing low-grade astrocytoma. The diagnosis typically is made by a combination of CT scan, MRI scan, and tissue biopsy.
There is no clear way to prevent the disease. Typically, treatment involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is used frequently as part of chemotherapy. High dose steroids may be used to help reduce swelling and decrease symptoms. It is unclear whether trying to remove all or simply most of the cancer is better.
Despite maximum treatment, the cancer usually recurs. The most common length of survival following diagnosis is 12 to 15 months, with fewer than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically three months. It is the most common cancer that begins within the brain and the second most common brain tumor, after meningioma. About 3 per 100,000 people develop the disease a year. It most often begins around 64 years of age and occurs more commonly in males than females. Immunotherapy is being studied.
Common symptoms include seizure, headaches, nausea and vomiting, memory loss, changes to personality, mood or concentration, and localized neurological problems.
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.