Primitive worm sheds new light on cancer

Our common evolutionary heritage with the humble nematode worm is helping unravel one of the key genetic puzzles in breast cancer, a new Cancer Research UK study¹ reveals.

For the first time, researchers have found a gene in the worm that is similar to the human breast and ovarian cancer gene BRCA1.

Scientists know BRCA1 plays an important role in human cells – repairing damaged DNA and stopping cancer from developing. But how it performs these functions remains a mystery.

Now they believe studying the gene in the worm will provide important insights into how breast and ovarian cancers develop and could pave the way to new treatments for the disease.

Previous studies have scanned the genomes of simpler organisms such as yeast, worms and flies for a gene similar to BRCA1 but have found nothing.

In the new study, scientists from the Cancer Research UK London Research Institute, in collaboration with researchers from America and Germany, performed a detailed search through the worm genome for genes that might be involved in repairing damaged DNA.

They stumbled on BRCA1 after they found a gene called BARD1. In humans BRCA1 and BARD1 form a complex, so when the team found BARD1 they knew they were close to discovering its partner.

Dr Simon Boulton, from the Cancer Research UK London Research Institute, says: “It’s nearly a decade since the BRCA genes were discovered and implicated in the development of breast and ovarian cancer but we are still very much in the dark about how they function.

“Previously, scientists have looked through the genome of the nematode worm but found no equivalent to the human BRCA1. So our new finding is somewhat unexpected but very exciting. The detailed genetic analysis we can do in cells of the worm is not really possible in more complex human cells.”

The soil-dwelling nematode worm, Caenorhabditis elegans, has less than a thousand cells and is around one millimetre in length. But, like us, it develops from embryo to adult and has a gut, nerves, muscles and skin. We also once shared a common ancestor so around 40 per cent of its genes are closely related to ours.

Dr Boulton says: “The nematode worm, is the focus of an intense research effort in both developmental biology and genetics because it is one of the simplest multi-cellular organisms with a nervous system.

“Studying a model organism like the worm can provide key insights into the way in which the more complex human genome works. Even though the worm set off on a different evolutionary path to us hundreds of millions of years ago, scientists can compare the worm and human genome to identify related genes. They can then use the simpler worm system to examine their function. It’s a fast and easy way to address some bigger questions about humans.”

Researchers analysed how the BARD1 protein behaves in the worm and found it interacted with a particular protein, which they believed to be the worm equivalent to human BRCA1.

To test whether the BARD1 and BRCA1 genes in the worm were involved in DNA repair they used a technique called RNA interference to separately switch off the genes while leaving all other genes unaffected.

They found many of the germ cells, which hold the reproductive components of an organism, died.

When they exposed the worms to radiation they detected even higher levels of cell death and many of their offspring failed to survive the treatment.

Dr Boulton says: “Our results show that these worm genes are involved in the DNA repair process and are essential for surviving DNA damage. This, along with the fact that the genes look similar to the human versions, tell us we’ve found the worm BRCA1 and BARD1.”

Professor Robert Souhami, Director of Clinical and External Affairs at Cancer Research UK, says: “Many important genes in humans are shared with the nematode worm which makes it an invaluable organism for genetic studies.

“Studying the BRCA1 counterpart in the worm will accelerate our understanding of how defects in this gene can lead to breast cancer and in the future will offer possibilities for prevention and treatment.”

ENDS

1. Current Biology14 (1)