NCI Cancer Bulletin for February 22, 2011 - National Cancer Institute: Common Genetic Deletion Found in Brain Cancers

Common Genetic Deletion Found in Brain Cancers


Researchers have identified a gene that is deleted in approximately one out of four patients with glioblastoma, the most common form of brain cancer. In addition, the researchers found that patients whose tumors had lost one copy of the gene, called NFKBIA, tended to have unfavorable outcomes. The results appeared in the February 17 New England Journal of Medicine and on the journal’s Web site in December.

Abnormalities in NFKBIA have been linked to other cancers, including Hodgkin lymphoma and multiple myeloma, but this study is the first to implicate defects in the gene in glioblastoma. NFKBIA appears to be a tumor suppressor gene; it produces a protein that normally helps to block growth-promoting messages from two signaling pathways linked to cancer, the NF-kappa B and the epidermal growth factor receptor (EGFR) pathways.

Approximately one-third of glioblastoma tumors have alterations in the EGFR gene, which can cause cells to proliferate and become cancerous. To identify additional genetic alterations in glioblastoma, the researchers profiled the EGFR and NFKBIA genes in tumors from nearly 800 patients with glioblastoma.

Based on an analysis of the results and additional laboratory experiments, the researchers concluded that the loss of NFKBIA is another way that glioblastoma cells can activate the NF-kappa B and EGFR pathways. The results also suggest that a majority of patients with glioblastoma have alterations in either EGFR or NFKBIA; very few tumors had abnormalities in both genes.

“We have identified a gene that is known to play a role in cancer, and there are substantial efforts under way to target that NF-kappa B pathway,” said lead author Dr. Markus Bredel of Northwestern University’s Feinberg School of Medicine. “So there are high hopes that we’ll be able to target this alteration.”

The researchers are developing a clinical test that could be used to detect the deletion in patients and potentially guide the selection of therapy in the future.

NCI Cancer Bulletin for February 22, 2011 - National Cancer Institute