Chemical Change in Gene Implicated in Lung Cancer  

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Posted: 1/5/2004

COLUMBUS, Ohio – Scientists are discovering mounting evidence linking a chemical change that turns genes on and off to the development of lung cancer and many other malignancies. The process is called methylation, a process that alters the activity of a gene, but not its structure.

Scientists used to think that virtually all cancer arose from mutations in the genes – tiny mix-ups in the sequence of all those so-called bases (adenine, cytosine, guanine and thymine, the A’s, C’s, G’s and T’s that make up DNA). And while it’s true that a mutation in even a single base can make a difference in the way a gene works – and may contribute to the growth of cancer – many scientists see methylation as an equally important part of the cancer puzzle.

Methylation is simply the addition of methyl molecules to particular sections of a gene marked by long stretches of C’s and G’s strung together. These long stretches are called CpG islands. When the methyl molecules are attached to CpG islands, they can act like brakes on a car, slowing and stopping a gene’s activity. Sometimes, this is helpful. During embryonic development, for example, cells use methylation to manage growth and tissue differentiation. But aberrant methylation can lead to cancer when it turns off important tumor suppressor genes the body needs to keep malignant cells from growing out of control.

Dr. Christoph Plass, a researcher at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, has spent years studying methylation and has found that some cancers have unique methylation patterns, like fingerprints.

Recently, Plass, along with Zunyan Dai, a doctoral student in the department of pathology at The Ohio State University, discovered that aberrant methylation of a gene called BMP3B (bone morphogenic protein 3B) is often involved in the development of non-small cell lung cancer.

Using a special technique called Restriction Landmark Genomic Scanning, a process that allows examination of up to 2,000 CpG islands at a time, they found that BMP3B was methylated in 47 percent of the 76 tumor samples they studied.

“This may be significant because BMP3B is involved in a signaling pathway that often malfunctions in the development of lung cancer,” says Plass.

For cancer researchers, one of the most intriguing aspects of methylation is that it can be reversed; newly developed drugs, like decitabine, appear to be able to turn on the genes that methylation has turned off. “We can’t do that with mutations,” says Plass.

Several other genes are also known to be frequently methylated in lung cancer, and all may be targets for therapeutic intervention.

Plass will be continuing research on methylation as a newly appointed member of an international team of scientists based at the Sanger Institute working on identifying methylation patterns in normal tissues on a genome-wide basis.

The National Cancer Institute and the V Foundation for Cancer Research sponsored Plass’ BMP3B research. Key colleagues on the study included Anthony Popkie, a graduate student in the Plass lab, and Dr. Gregory Otterson, a lung cancer specialist at The James.

The Ohio State University Comprehensive Cancer Center is a network of interdisciplinary research programs comprising over 200 investigators in 13 colleges and the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute on the OSU campus. OSUCCC members conduct research on the prevention, detection, diagnosis and treatment of cancer, generating over $75 million annually in external funding.

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Michelle Gailiun
Medical Center Communications

Tags: Basic Research; Cancer; James Cancer Hospital; Lung Cancer

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) 460 W. 10th Avenue, Columbus, OH 43210 Phone: 1-800-293-5066 | Email: