Genetic map identifies close to 200 cancer genes

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The first genetic map of colon and breast cancer shows that nearly 200 mutated genes—most of them previously unknown—help tumors start, grow and spread, U.S. researchers reported on Thursday.

The findings could lead to new treatments for cancer, better ways to diagnose it, and certainly will provide insights into the second-leading cause of death in the developed world, the researchers said.

Dr. Kenneth Kinzler of Johns Hopkins University in Baltimore, who helped lead the study, said it showed that cancer was more complex than even experts in the genetics of the disease had believed. 

"There are a lot of mutated genes,” Kinzler said in a telephone interview.

“A lot of things seem to have gone wrong.”

“We expected to find a handful of genes, not 200,” added Tobias Sjoblom, the principal author of the study.

The researchers said they had identified 189 genes—with an average of 11 per tumor—that were clearly mutated in breast and colon tumors.

“The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion,” they wrote in their report published in the journal Science.

The team, including researchers at the University of South Carolina and Case Western Reserve University in Cleveland, looked at 11 samples each from breast and colon tumors surgically removed from patients.

“These cancers were chosen for study because of their substantial clinical significance world-wide: together, they account for about 2.2 million cancer diagnoses (20 percent of the total) and about 940,000 cancer deaths each year (14 percent of the total),” they wrote.

CANCER GENOME ATLAS

The study could help guide a National Institutes of Health project started last December to map all the genes involved in cancer, Kinzler said.

“We anticipate that as The Cancer Genome Atlas scales up, we may be able to identify the majority of genetic changes that cause the most important and common forms of the major cancers,” National Human Genome Research Institute Director Dr. Francis Collins said in a statement commenting on the research.

“In fact, the large number of mutations reported in this paper offers a glimpse of what is yet to come and provides exciting new directions for drug discovery in breast and colon cancer.”

Traditional chemotherapy affects fast-growing cells, which include both tumors and healthy cells. Newer drugs, such as Herceptin, Gleevec and Iressa target specific genes.

The targeted therapies only help a fraction of cancer patients, however, and doctors knew that many more genes must be involved in cancer.

“Almost any gene could be considered a drug target,” Kinzler said.

“We are convinced that this kind of study will provide one of the best road maps possible for beating cancer. Who would pass up the opportunity to read the enemy’s game plan?” he said.

The study could also help provide more personalized therapy.

“Each cancer has a different blueprint,” said Dr. Victor Velculescu at Johns Hopkins. “No two patients are identical.”

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