For more than 100 years, researchers have been unable to explain why cancer cells contain abnormal numbers of chromosomes, a phenomenon known as aneuploidy. Many believed aneuploidy was simply a random byproduct of cancer.
Now, a team at Harvard Medical School has devised a way to understand patterns of aneuploidy in tumors and predict which genes in the affected chromosomes are likely to be cancer suppressors or promoters. They propose that aneuploidy is a driver of cancer rather than a result of it.
The study, to be published online in Cell on Oct. 31, offers a new theory of cancer development and could open the door for new treatment targets.
"If you look at a cancer cell, it looks like an unholy mess with gene deletions and amplifications, chromosome gains and losses, like someone threw a stick of dynamite into the cell. It seems random, but actually previous work has shown that there is a pattern to which chromosomes and chromosome arms are alteredand that means we can understand that pattern and how or if it drives cancer," said senior author Stephen Elledge, Gregor Mendel professor of Genetics and of Medicine at HMS and professor of medicine at Brigham and Women's Hospital.
"What we have done is to propose a new theory about how this works and then prove it using mathematical analysis," he said.
Mining for answers
For decades since the "oncogene revolution," cancer research has focused on mutationschanges in the DNA code that abnormally activate genes that promote cancer, called oncogenes, or deactivate genes that suppress cancer. The role of aneuploidyin which entire chromosomes or chromosome arms are added or deletedhas remained largely unstudied.
Elledge and his team, including research fellow and first author Teresa Davoli, suspected that aneuploidy has a significant role to play in cancer because missing or extra chromosomes likely affect genes involved in tumor-related pro
|Contact: David Cameron|
Harvard Medical School