August 9, 2011
Mapping Genes for Brain Cancer
(Ivanhoe Newswire) "“ Scientists have completed a map of genetic mutations occurring in the second-most common form of brain cancer, oligodendroglioma. The findings appear to reveal the biological cause of the tumors. Oligodendroglioma accounts for up to 20 percent of brain cancers and more commonly occur in younger people and 30 to 45.
To create the map, the scientists sequenced protein-coding genes in seven oligodendroglioma tissue samples, and focused attention on recurring mutations in two genes not previously associated with these tumors "“ CIC and FUBP1. The investigators say that CIC and FUBP1 are known to regulate cell-signaling processes, and CIC mutations have been rarely linked to sarcoma, breast and prostate cancers.
More mutations in the two genes were found in an additional 27 oligodendroglioma samples. In all, two-thirds of the samples studied had CIC and FUBP1 mutations.
"Whenever we find genes mutated in a majority of tumors, it is likely that the pathway regulated by that gene is critical for the development and biology of the tumor," Nickolas Papadopoulos, Ph.D., associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, was quoted as saying.
In brain cancer, the Hopkins investigators say CIC and FUBP1 mutations may be the "missing link" in what scientists describe as a "two-hit" theory of cancer development. The theory is based on the fact that each cell in the human body has two copies of 23 chromosomes containing thousands of protein-producing genes. If a gene on one chromosome is damaged or deleted, the other copy makes up for the loss of protein. But if the second copy fails as well, the cell cannot make the proper protein and may become cancerous.
In oligodendrogliomas, the "first hit" has long been known to occur in regions of chromosome 1 and 19, which fuse together resulting in a loss of many genes on both chromosomes. Up to 70 percent of oligodendroglioma patients have these DNA fusions, and most of them respond better to chemotherapy and radiation than those who lack the deletions in the chromosomes. For more than a decade, researchers have been looking for evidence of a "second hit" in specific mutated genes that allow oligodendrogliomas to develop.
In the current study, the Johns Hopkins investigators found mutations in the remaining copies of the CIC and FUBP1 genes on chromosomes 1 and 19, suggesting that these mutations represent the second hit needed to create cancer.
"Thanks to the Human Genome Project and advances in cancer genome sequencing, a single study can now resolve decade-old questions and reveal the genetics of this brain cancer," Kenneth Kinzler, Ph.D., professor and co-director of the Ludwig Center at Johns Hopkins, was quoted as saying. "Knowing the genetic roadmap of a cancer is the key to attacking it."
SOURCE: Science, published online August 9, 2011