Far more mutations than thought involved in cancer

WASHINGTON Wed Mar 7, 2007 4:21pm EST

A magnified (20x) stained section of a clear cell renal cancer. A painstaking scan of the DNA of tumor cells shows hundreds of previously unsuspected genes are involved in cancer, researchers said on Wednesday in a finding that offers new ways to fight the disease. REUTERS/Dr Bin Teh, Van Andel Research Institute/Handout

A magnified (20x) stained section of a clear cell renal cancer. A painstaking scan of the DNA of tumor cells shows hundreds of previously unsuspected genes are involved in cancer, researchers said on Wednesday in a finding that offers new ways to fight the disease.

Credit: Reuters/Dr Bin Teh, Van Andel Research Institute/Handout

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WASHINGTON (Reuters) - A painstaking scan of the DNA of tumor cells shows hundreds of previously unsuspected genes are involved in cancer, researchers said on Wednesday in a finding that offers new ways to fight the disease.

They found more than 1,000 different mutations in just one family of genes taken from 200 samples of breast, stomach, colorectal and other common tumors. Other groups of genes also are involved in cancer.

"We find evidence for approximately 100 new cancer genes," Dr. Mike Stratton, co-leader of the Cancer Genome Project at the Sanger Institute in Cambridge, Britain, told reporters.

He said 120 of the mutations in these genes are believed to be "driver" mutations that directly contribute to the development of cancer.

"We call them drivers because they drive a cell to stop behaving normally and drive them to behave like cancer cells," Stratton told the telephone briefing.

"This is a lot larger number of cancer genes than we really expected to find," added the Sanger Institute's Dr. Andrew Futreal, who also worked on the study, published in this week's issue of the journal Nature.

"I would have guessed it would have been no more than 10, probably, given what we knew."

The researchers chose a family of genes that are known to be involved in cancer, the kinases. Kinases are the basis of some of the new targeted cancer therapies that have had stunning results in a small number of patients.

Kinases can act as relays, switching cells on and off.

The researchers compared the genetic sequences of cells taken from tumor samples from cancer patients to the DNA in normal, healthy cells, and tracked down every mutation.

"Some cancers had a lot of mutations. Other cancers had very few," Stratton said.

DECADES OF DAMAGE

In some, the reasons are clear. For instance, lung cancer tumors had many mutations -- the result of years of smoking damage.

"The mutations that we encounter in a cancer are like an archeological record of what that cancer cell has been through in its lifetime," Stratton said.

Lung carcinomas had the most mutations, followed by gastric cancers, ovarian cancers and colorectal cancers. Testicular cancer tumors and most breast cancers carried few mutations.

The researchers also found a large number of what they call "passenger" mutations.

"These are mutations that are also present in the cancer cell but they appear to have nothing to do with the causation of the cancer -- they just appear to hitchhike along for the ride," Stratton said.

The researchers said this was an early look at the causes of cancer and said much more study is needed. But scientists can begin to use the information to design better drugs.

In a second study in the same journal, Dr. James Downing of the St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues identified genetic mutations in patients with acute lymphoblastic leukemia, or ALL.

They surveyed the genomes of leukemia cells from 242 children with ALL.

They found unexpected mutations in genes encoding regulators of B-cell development and differentiation in 40 percent of a type of ALL called B-progenitor ALL. B-cells are immune system cells that are affected by ALL.

"The most common targets of these genetic alterations (genes called EBF1, PAX5 and IKZF1) have central roles in the development of normal B-cells," the researchers wrote.

To fully understand cancer, scientists will have to catalog, in detail, every genetic mistake involved in that cancer, they said. "The data presented in this paper provide a rational 'road map' for approaching such a task," they wrote.

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