Gene Imprinting Discovery May Aid Cancer Treatment : Science: Finding suggests that in some cases it may not be necessary to destroy diseased cells. Instead, it might be possible to ‘reason with them or educate them.’

Biologists have found an exception to one of the most fundamental rules of genetics, a discovery that promises to provide new approaches to the control of cancer and other genetic diseases.

Researchers say the finding suggests that cancer could be combatted by restoring a simple process called imprinting, rather than by trying to repair a defective tumor gene.

“This implies that, in some situations, it may not be necessary to kill cancer cells. It might be possible to reason with them or educate them,” said Samuel Broder, director of the National Cancer Institute.

For 130 years, since the Austrian monk Gregor Mendel first studied inheritance by breeding peas, scientists have assumed that the source of a gene, the fundamental unit of inheritance, is irrelevant. Everybody inherits two copies of most genes, one from each parent. A healthy gene from the mother, researchers have confidently believed, is identical to a healthy gene from a father.

But recent research in plants and animals has shown that this is not always true. Employing a phenomenon called imprinting, some genes seem to “remember” which parent they come from and the copy from one parent is inactivated.

A report today in the British journal Nature extends the exception to humans. Researchers from the University of Michigan say they have identified specific imprinted genes in people for the first time.

The gene for a protein called insulin-like growth factor 2 is normally imprinted in people, said Dr. Andrew Feinberg, a medical geneticist at Michigan. The imprinted IGF2 gene from the mother is normally not active in the child, but when it loses that imprinting and becomes active, it leads to a form of childhood cancer called Wilm’s tumor. Feinberg’s results were corroborated in separate papers by British and Australian researchers.

If the imprinting is defective, he has found, the child’s cells have two working copies of a healthy gene and cancer results. This is “a radical concept in genetics,” Feinberg said, because scientists have never before observed cancer caused by healthy genes.

Researchers also suspect that the same type of process might cause a variety of other genetic diseases. “The jury is still out on that . . . but my suspicion is that it is probably more common than we think,” Broder said.

This phenomenon “is going to be much more important than anyone would have predicted a couple of years ago,” added cell biologist Tim Bestor of Harvard University.

Although this is the first time the phenomenon has been linked to specific genes, it has been observed before with chromosomes, larger units of inheritance that contain thousands of genes. “No one has ever before found a gene in man that has been imprinted,” Feinberg said. “This is the first time it has been nailed down at the gene level.”

Feinberg says his results may have widespread applicability. “A large number of childhood tumors show increased IGF2 (production), and it’s thought to be important in breast, colon and lung tumors in adults,” he said. “We know that if you block IGF2 (production), some tumors don’t grow. My guess is that the (defectiveness) of imprinting will turn out to be a widespread alteration involved in many tumors.”

Feinberg and others are now trying to determine how imprinting occurs. Evidence in animals suggests that suppression of a gene’s normal activity occurs when individual components of the gene are chemically altered by a process called methylation, and most assume that the mechanism will be the same in humans.

“One of the things that excites me the most is that this process is reversible,” Feinberg said. “It is easier for me to imagine some kind of way to change that imprint and put a cancer back in a normal state than to replace a defective gene in a tumor.”

But, cautioned Broder: “We shouldn’t expect a practical application overnight. It’s a very interesting basic science observation, but it is going to take a lot of development before it is useful.”