After over a decade of research, the hunt for the genetic causes of chordoma has reached an important milestone with the discovery of a gene linked to familial chordoma. In a paper published today in Nature Genetics, investigators at Duke University and the National Cancer Institute report that duplication of the gene brachyury is a cause of familial chordoma.
Other inherited cancer syndromes are caused by mutations (misspellings in a gene), or gene deletion, but familial chordoma is the first linked to an extra copy of an entire gene. This groundbreaking discovery is potentially paradigm-shifting for cancer genetics, as it may indicate that gene amplification could be a risk factor for other types of cancer as well.
According to Michael Kelley, MD, whose lab analyzed the DNA of familial chordoma patients, “this discovery is a classic example of where science answers one question but raises many, many more.” Questions such as: why does brachyury amplification cause susceptibility to chordoma? is brachyury amplified in sporadic (non-familial) chordomas? do chordomas depend on brachyury to survive? can the effect of brachyury amplification be reversed? does reversing brachyury amplification kill chordoma cells?
While this discovery represents a major advance in the understanding of chordoma biology, only by answering these questions will researchers be able to determine what implications it has for the treatment of chordoma.
The first clue as to the importance of brachyury in chordoma came in 2006 from researchers at University College London who reported that brachyury was highly expressed in virtually all chordomas. Because of the critical role brachyury plays in the development the notochord – the embryonic tissue from which chordoma is derived – some researchers have postulated that brachyury may be important for the development of chordoma. Research is already ongoing in several labs to understand the role that brachyury plays in chordoma, and this latest discovery will surely add renewed vigor and urgency to those projects, and spark numerous new projects.
The Chordoma Foundation salutes and thanks all the researchers involved in the familial chordoma study who have devoted so many years of their careers to uncovering the genetic mysteries of chordoma. We are glad to have be able to support Dr. Kelley’s lab over the past year, and are grateful to the donors who made this support possible.