Chordoma Foundation

Breaking news: Genetic risk factor for chordoma identified

Foundation-funded research yields major discovery that could open door to new therapies

For the first time ever, scientists have identified a specific genetic risk factor that, when present, significantly increases the chances that an individual will develop chordoma.

This discovery – a milestone outcome of the Chordoma Foundation’s significant investment in the Chordoma Genome Project over the past three years – provides unprecedented insight into how chordoma forms, and potentially how to effectively treat it.

A team of scientists at University College London (UCL), Royal National Orthopedic Hospital (RNOH), and the Sanger Institute found that over 95% of Caucasian chordoma patients have a variation (an A substituted for a G) in the DNA sequence at a particular site on the brachyury gene (also known as the T gene). The study found that people with the A version of the brachyury gene are just over five times more likely to develop chordoma than the general population.

The groundbreaking discovery is published in the high-profile scientific journal Nature Genetics. An electronic version of the paper is accessible online ahead of publication:

“Our finding that this variation is associated with a five-fold increase in the risk of developing chordoma is remarkable in cancer genetics, as almost all other genetic variants associated with cancer cause only a modest (less than two-fold) increase in risk,” explains Dr. Adrienne Flanagan of UCL, who led the study. “This study makes a strong case that this particular variation in the brachyury gene contributes significantly to the development of chordoma in nearly all patients. It is a major step forward in our understanding of how chordoma develops, and can open the door to the development of an effective, targeted treatment.”

Brachyury has previously been implicated in chordoma and several other types of cancer. Most notably, in 2009, scientists found that inheriting an extra copy of brachyury is responsible for causing familial chordoma. Individuals with familial chordoma receive three copies of this gene rather than the two copies normally inherited, one each from mother and father. This latest finding confirms that the brachyury gene also plays a central role in the more typical sporadic (non-familial) version of the cancer.

However, alteration of the brachyury gene does not appear to be solely responsible for causing chordoma. Nearly 40% of the worldwide population has the A version of brachyury, yet the vast majority will never get chordoma; even for individuals with the A version, the chances of developing chordoma are less than two in a million. This indicates that while the altered version of brachyury may load the gun, something else pulls the trigger.

Upcoming research will focus on understanding why the alteration in brachyury is so critical for chordoma development, and what other factors are at play. Answering these questions may enable scientists to develop an effective treatment that reverses or blocks the effect of the alteration.

Moving forward: funding the next stage of research

Finding a genetic variation that is so strongly associated with chordoma raises important questions and creates a number of opportunities to further advance the understanding and treatment of chordoma

The research team at UCL and the Sanger Institute is poised to launch the next phase of the Chordoma Genome Project, which will attempt to determine what actually triggers the development of chordoma once the brachyury variation sets the stage. This project is ready to start as soon as the Chordoma Foundation can raise $47,000 to fund this work.

When investigators gather at the Fourth International Chordoma Research Workshop in March 2013, discussing how to follow up on this discovery will be at the top of the agenda. The Foundation aims to raise $250,000 as soon as possible to fund seed grants that will be critical to allow researchers to pursue ideas and plans that emerge from the workshop.

In the meantime, the Foundation will continue to share outcomes of the Chordoma Genome Project and developments that flow from this genetic discovery as they happen.

For more detailed information about this discovery and what it means for chordoma patients and families click here. To provide immediate funding needed for the next phase of this research, please donate here or contact Chordoma Foundation Executive Director Josh Sommer at

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