Gene deletion may explain many cases of glioblastoma
An important gene deletion appears to occur in as many as 1 of every 4 cases of glioblastoma—the most common adult brain cancer—scientists have found.
The NFKBIA gene is normally present on chromosome 14. Defects in the gene have been found in Hodgkin lymphoma; multiple myeloma; melanoma; and breast, lung, and colon cancers. Now, a team of investigators led by Griffith Harsh, MD, professor of neurosurgery at Stanford University School of Medicine, has implicated the deletion of a copy of NFKBIA as a contributor to glioblastoma. This deletion adds to tumor development, promotes resistance to therapy, and worsens survival prospects.
According to a statement issued by Stanford University Medical Center, the deletion of NFKBIA triggers biochemical processes similar to those resulting from a better-known aberration common in glioblastomas: alteration of the epidermal growth factor receptor, or EGFR. At least a third of glioblastomas feature an abnormality in the gene coding for EGFR.
The researchers found that a surprisingly high proportion of tumor samples—25%—collected from glioblastoma patients over the course of 10 years demonstrated NFKBIA deletions. Approximately a third of the samples exhibited EGFR aberrations, with both gene aberrations occurred together in only about 5% of the samples.
The new NFKBIA findings, published online by The New England Journal of Medicine (www.nejm.org/doi/pdf/10.1056/NEJMoa1006312), may eventually help improve prognosis and treatment of glioblastoma—for example, the tumor potentially could be targeted with drugs that stabilize I-kappa-B, the protein product of NFKBIA.