News and events

01/02/13

Research - what have we achieved so far

In 2006, Professor Adrienne Flanagan, from UCL Cancer Institute and The Royal National Orthopaedic Hospital, identified that chordomas express a marker known as brachyury, otherwise known as T. Brachyury, is involved in the normal development of the fetal notochord, a rod-like structure which turns into the intervertebal discs and vertebral bodies in the mature fetus. However, until this discovery, it was thought that this gene, brachyury, was expressed only in the embryo fetus and that it disappeared before birth. The origin of chordoma had perplexed pathologists for more than 200 years, and the link made between chordoma and brachyury finally confirmed that chordoma was a notochordal tumour. This was the first breakthrough in understanding the disease, and potentially holds the key to new treatments. Professor Flanagan showed that brachyury was expressed in virtually all chordomas and could be used as a biomarker, and would help pathologists in making the diagnosis of this cancer. Before this, it was difficult for pathologists to distinguish chordoma from some other cancers such as chondrosarcoma, and carcinoma (a much more common form of cancer) for which the treatments are different. Brachyury is now recognised as the hallmark of the disease and is used globally for diagnosing this rare tumour. Professor Flanagan's research team then showed that brachyury was required for the chordoma cells to grow / multiply. They achieved this by silencing / 'turning off' brachyury in chordoma cells in the laboratory. They also found that brachyury is a master regulator of other genes that make cells grow and migrate. Hence, if brachyury is 'silenced' many of the genes downstream of it are also silenced. There is also some more recent evidence that the expression of brachyury may also play a role in some lung and colon cancers. There are also other reasons for implicating brachyury in the development of chordoma. Those rare patients who have a family history of chordoma, carry a genetic abnormality in the brachyury gene. Furthermore, Dr Nischalan Pillay in Prof Flanagan's team showed 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. Professor Flanagan's team now believe that it is important to 'silence' brachyury in the tumour cells if the disease is to be controlled.

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There is little funding available for research into this relentless bone cancer mainly because it is relatively rare, occurring in only 1 in 800,000 of the population. Without a focused approach to raising money for research into chordoma, little will change quickly.

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