Johns Hopkins scientists map genes for common form of brain cancer of the

Johns Hopkins Kimmel Cancer Center scientists have an extensive map of genetic mutations that occur in the second most common form of brain cancer, oligodendroglioma completed. The findings, in the August 4 issue of science, reported also seem to reveal the biological cause of the tumors, they say.

To create the map, the scientists sequenced protein-coding genes in seven oligodendroglioma tissue samples, and focus on recurring mutations in two genes not previously associated with these tumors CIC and FUBP1. The researchers say that CIC and FUBP1 have been known to cell signaling processes and CIC mutations are rarely linked to cancer of the Sarcoma, breast and prostate cancer.

More mutations in two genes were found in an additional 27 oligodendroglioma samples. In all had two-thirds of the samples studied CIC and FUBP1 mutations.

"When we find genes mutated in a majority of tumors, it is likely that the trajectory that regulated gene is of crucial importance for the development and the biology of the tumor," says Nickolas Papadopoulos, Ph.d., Professor of Oncology at the Johns Hopkins Kimmel Cancer Center.

In the brain cancer say the Hopkins researchers with CIC and FUBP1 mutations can the "missing link" in what scientists as a "two-hit" theory of development of cancer. The theory is based on the fact that each cell in the human body has two copies of the 23 chromosomes with thousands of protein-producing genes. When a gene on a chromosome is damaged or deleted, the other copy for the loss of protein. But if the second copy as well fails, the cell cannot make the correct protein and cancer can be.

In oligodendrogliomas, is the "first hit" has long been known to occur in regions of chromosome 1 and 19, which melt together, resulting in a loss of many genes on both chromosomes. Up to 70% of oligodendroglioma patients have this DNA mergers, and most of them respond better to chemotherapy and radiation than those who do not have the deletions in chromosomes. For more than a decade, researchers have been looking for evidence of a ' second hit "in specific mutated genes that make it possible to develop oligodendrogliomas.

In the current study, researchers from the Johns Hopkins found mutations in the remaining copies of the CIC and FUBP1 genes on chromosomes 1 and 19, suggesting that these movements represent the second single of cancer.

"Thanks to the human genome project and advances in cancer genome sequencing, a single research can now solve the decade-old questions and reveal the genetics of this brain cancer," says Kenneth Kinzler, Ph.d., professor and Co-Director of the Ludwig Center at Johns Hopkins. "Know the genetic roadmap of a cancer is the key to the attacks."

Oligodendrogliomas account for up to 20% of the brain cancer and occur more commonly in younger people 30 to 45 years. The cancers usually in the frontal lobe of the brain cells that coat neurons. Median survival of 10 years is considered much better than other forms of brain cancer. Oligodendrogliomas are initially treated with surgery, followed by chemotherapy and radiation.

The research team says its next step will be to test whether patients with CIC and FUBP1 mutations the same favourable prognosis as those who have the merger of chromosome 1 and 19, says Chetan Bettegowda, M.D., Ph.d., chief resident in the Department of neurosurgery at Johns Hopkins.

"We can now focus on when these movements during the formation of tumor development, or they may accompany forecast, and how can they constitute objectives for therapy," says Bettegowda.

Bettegowda says the map discovered gene mutations in other genes, such as PIK3CA, who has been well-studied in cancer. It is possible, he says, that oligodendroglioma patients with PIK3CA mutations in other genes or in current clinical trials using experimental therapies aimed at these mutations could be registered.

Source: Johns Hopkins Medicine