A comprehensive map of genetic mutations occurring in the second-most common form of brain cancer, oligodendroglioma, appears to reveal the biological cause of the tumors, scientists say.
They created the map by sequencing protein-coding genes in seven samples of tissue from oligodendroglioma tumors, and concentrated on recurring mutations in two genes (CIC and FUBP1) not previously associated with those types of tumors.
The genes appear to be the missing link in the “two-hit” theory of cancer development, the scientists said.
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.
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.
The study was recently published in the journal Science.