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Genes' 'On/Off' Switches Yield Clues to Breast Cancer

By Amanda Gardner
HealthDay Reporter

WEDNESDAY, March 23 (HealthDay News) -- Scientists may have developed a new way of predicting when breast cancer will spread.

Two varieties of what scientists call "epigenetic signatures" seem to distinguish more aggressive cancers from less aggressive ones, according to a new study.

Epigenetic alterations do not involve changes to the sequencing of the genes themselves. Instead, they involve alterations in the outer wrapping that holds genes within the chromosome. This chromosomal casing helps determine whether the genes will activate and at what intensity.

Environmental factors, including diet, stress, illness or environmental pollutants can all influence epigenetics, experts note.

The findings could not only lead someday to a new diagnostic screening tool to parse out more aggressive cancers that might benefit from more aggressive treatment, but could also "open the door for new physiological targets" for therapies, explained Dr. Timothy A. Chan, senior author of a paper appearing March 23 in the journal Science Translational Medicine.

It's also not out of the question that modifiable environmental factors might be identified that contribute to the cancers, Chan said.

How to tell if a particular tumor will spread (metastasize), and then finding ways to prevent that are major goals of the researchers. Patients usually die from a cancer that has metastasized, not from localized tumors.

This international consortium of researchers collected a variety of different types of breast cancers -- some were hormone receptor-positive, some negative, some had spread and some had not -- then analyzed their methylation profiles.

Methylation refers to the epigenetic "marks" left on the genome.

"To our surprise, we noted that there appear to be two main epigenomic subgroups," said Chan, who is a lab head and attending physician at Memorial Sloan-Kettering Cancer Center in New York City.

This was a surprise because scientists have identified myriad different types of breast cancers based on their genetics and other characteristics.

In this case, one group showed high methylation and one showed low.

The high-methylation group "tended to be pretty stable at the genomic level and were composed primarily of hormone-positive cancers," Chan said. "The [low-methylation] group includes all the hormone-negative group and about half of hormone-positive cancers."

And women with high-methylation tumors did much better than the other group, independent of their hormone-receptor status.

The team is now working on a test to distinguish the two epigenetic types and are investigating what drives these changes, which have also been observed in colon cancer and the deadly brain cancer glioblastoma.

"What we're probably looking at is some fundamental process that becomes dysregulated and helps drive the cancers," Chan said.

"This [study] allows us to further subset breast cancers into those that are likely to metastasize and those that aren't likely to metastasize, and that's helpful," noted one expert, Dr. Patrick Borgen, chairman of the department of surgery at Maimonides Medical Center in New York City.

But, Borgen cautioned, "the technology that [does this categorization] is far from the grasp of day-to-day clinicians. [The study is] an important foundation for further research."

More information

Learn more about epigenetics at the University of Utah.

SOURCES: Timothy A. Chan, M.D., Ph.D., lab head and attending physician, Memorial Sloan-Kettering Cancer Center, New York City; Patrick Borgen, M.D., chairman, department of surgery, Maimonides Medical Center, New York City; March 23, 2011, Science Translational Medicine

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