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Rogue DNA drives cancer growth

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Long terminal repeats (LTRs) are a form of ‘junk DNA,’ genetic material that has accumulated in the human genome over millions of years. Although LTRs originate from viruses and are potentially harmful, they are usually made inactive when embryos are developing in the womb. A new international research collaboration demonstrates for the first time that if the inactivation doesn’t work, the LTRs can activate cancer genes. (Credit: iStockPhoto)

U. LEEDS (UK)—Junk DNA promotes the growth of cancer cells in patients with Hodgkin’s lymphoma and may play a role in other forms of cancer as well.

The DNA, called “long terminal repeats” (LTRs), are a form of genetic material that has accumulated in the human genome over millions of years. Although LTRs originate from viruses and are potentially harmful, they are usually made inactive when embryos are developing in the womb.

A new international research collaboration demonstrates for the first time that if the inactivation doesn’t work, rogue active LTRs can drive the growth of cancer in humans.

“We have shown this is the case in Hodgkin’s lymphoma, but the exact same mechanism could be involved in the development of other forms of blood cancer,” says Constanze Bonifer, professor at the University of Leeds. “This would have implications for diagnosis, prognosis, and therapy of these diseases.”

Details of the work are described in the journal Nature Medicine.

The research focused on cancerous cells of Hodgkin’s lymphoma (the Hodgkin-/Reed Sternberg cells) that originate from white blood cells (antibody-producing B cells). Researchers found that the lymphoma cells’ growth was dependent on a receptor that normally regulates the growth of other immune cells, but it is not usually found in B-cells.

However in this case, the Hodgkin-/Reed Sternberg cells “hijacked” this receptor for their own purposes by activating some of the ‘junk DNA’.

In fact the lymphoma cells activated hundreds, if not thousands, of LTRs all over the genome, not just one.

Hodgkin-/Reed Sternberg cells may not be the only cells that use this method to subvert normal controls of cell growth. The researchers found evidence of the same LTRs activating the same growth receptor in anaplastic large cell lymphoma, another blood cancer.

The consequences of such widespread LTR activation are currently still unclear, but such processes could potentially activate other genes involved in tumor development.

It could also affect the stability of chromosomes of lymphoma cells, a factor that may explain why Hodgkin-/Reed Sternberg cells gain many chromosomal abnormalities over time and become more and more malignant.

Researchers from the Charité University Medical School and the Max Delbrück Centre  for Molecular Medicine (MDC) in Berlin, Germany, contributed to the study.

More University of Leeds news: www.leeds.ac.uk/news

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