Clusters of tiny chemical changes to DNA may help push normal brain cells to become cancerous, according to City of Hope researchers. The finding could point the way to blood tests for screening at-risk patients as well as to potential treatments.
The research appeared in the April 1 issue of Cancer Research.
|Gerd Pfeifer and his team found chemical changes to DNA that provide clues about a type of brain cancer. (Photo by Paula Myers)|
Researchers led by Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology and chair of the Department of Cancer Biology, studied cancerous cells from patients with a common and often lethal type of brain tumor called astrocytoma. They were looking for genes with a specific chemical change called methylation. Methylation is a way that cells can control genes, and scientists have shown that certain methylation patterns are associated with cancer.
In methylation reactions, cells place small caps called methyl groups on their chromosomes. Adding or removing the methyl groups at various points on the chromosomes turns genes on or off. Placing methyl groups at the start of a gene switches the gene off; placing them in the middle of the gene boosts the gene’s activity.
Often, cells place methyl groups on chromosomes at places called CpG islands, which are lengths of DNA code that have high amounts of the same two pieces of the genetic code.
Pfeifer and his team found that brain tumor cells had more methyl groups on many of their CpG islands than normal brain cells did. In particular, these highly methylated CpG islands appeared in many genes involved in brain cell growth and development. This led the researchers to believe methylation may be key to turning normal brain cells cancerous, which would advance current understanding of the origins of astrocytoma.
The team noted several hundred CpG islands in brain tumor cells that had many more methyl groups than were seen in normal brain cells. The heavily methylated islands were scattered across many chromosomes, but the same 428 highly methylated CpG islands were found in 25 percent or more of the brain tumor samples. They also found locations on chromosomes where many consecutive CpG islands were over-methylated.
According to Pfeifer, those hypermethylated locations could serve as flags or signposts of cancer, even at the disease’s earliest stages, potentially leading the way to improved diagnostic and treatment methods.
“Searching for the commonly hypermethylated CpG islands may tell us something about the mechanisms how these tumors arise,” Pfeifer said. The islands also might show how a patient might respond to treatment, he added.
Further research will help give clues about possible preventive measures and potential new treatment methods, as well, Pfeifer said.
The National Institutes of Health funded the research, which was conducted by a team of researchers at Beckman Research Institute of City of Hope and colleagues in Chicago, England and Germany.