At a glance:
- Researchers trace the origin of certain breast cancers to genomic reshuffling — rearrangement of chromosomes — that activates cancer genes and ignites disease.
- The finding offers a long-missing explanation for many cases of the disease that remain unexplained by the classical model of breast cancer development.
- The study shows the sex hormone estrogen — thus far thought to be only a fuel for breast cancer growth — can directly cause tumor-driving genomic rearrangements.
In what may turn out to be a long-missing piece in the puzzle of breast cancer, Harvard Medical School researchers have identified the molecular sparkplug that ignites cases of the disease currently unexplained by the classical model of breast-cancer development.
“We have identified what we believe is the original molecular trigger that initiates a cascade culminating in breast tumor development in a subset of breast cancers that are driven by estrogen,” said study senior investigator Peter Park, professor of biomedical informatics in the Blavatnik Institute at HMS.
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The researchers said as many as one-third of breast cancer cases may arise through the newly identified mechanism.
The study also shows that the sex hormone estrogen is the culprit behind this molecular dysfunction because it directly alters a cell’s DNA.
Most, though not all, breast cancers are fueled by hormonal fluctuations. The prevailing view of estrogen’s role in breast cancer is that it acts as a catalyst for cancer growth because it stimulates the division and proliferation of breast tissue, a process that carries the risk for cancer-causing mutations. The new work, however, shows that estrogen causes mischief in a far more direct manner.
“Our work demonstrates that estrogen can directly induce genomic rearrangements that lead to cancer, so its role in breast cancer development is both that of a catalyst and a cause,” said study first author Jake Lee, a former research fellow in the Park lab who is now a medical oncology fellow at Memorial Sloan Kettering Cancer Center.
Although the work has no immediate implications for therapy, it could inform the design of tests that can track treatment response and could help doctors detect the return of tumors in patients with a history of certain breast cancers.
Birth of a cancer cell
The human body is made up of hundreds of trillions of cells. Most of these cells are constantly dividing and replicating, a process that sustains the function of organs day after day, over a lifetime.
With each division, a cell makes a copy of its chromosomes — bundles of tightly compressed DNA — into a new cell. But this process sometimes goes awry, and DNA can break. In most cases, these DNA breaks get swiftly mended by the molecular machinery that guards the integrity of the genome. However, every now and then, the repair of broken DNA gets botched, causing chromosomes to get misplaced or scrambled inside a cell.