DNA mutation likened to lit fuse in kids with cancer syndrome

Certain DNA changes may help predict which patients with an inherited genetic syndromeare at higher risk of developing tumours earlier in life.

Li-Fraumeni Syndrome or LFS is a familial cancer syndrome that predisposes children and young adults to develop cancers, commonly of the brain, bone, breast and soft tissue.

'This discovery could potentially provide a reliable way to assess the risk and the appropriate screening tests for carriers of LFS.' Lead researcher Dr. David Malkin

Researchers at Toronto's Hospital for Sick Children found that the rate of shortening of the ends of chromosomes, or telomeres, in the white blood cells of people with the syndrome may help predict the onset of tumour development.

Their study appears in Thursday's issue of the journal Cancer Research.

It's as if the telomeres in affected people act like a lit fuse, the researchers said.

The length of telomeres shrink every time a cell divides, like a chromosomal clock that reflects the aging process.

Scientists suspect that as telomeres shrink, chromosomes become less stable and are therefore more likely to mutate.

The team found that telomere length was much shorter in children with the syndrome and cancer than in their siblings who were free of cancer.

"One of the challenges of caring for patients with Li-Fraumeni syndrome is the unpredictable and varying ages at which cancer may develop," says lead researcher Dr. David Malkin, co-director of the Cancer Genetics Program at Sick Kids.

"This discovery could potentially provide a reliable way to assess the risk and the appropriate screening tests for carriers of LFS."

Clue to earlier cancers

Malkin and his colleagues analyzed blood samples from members of nine families with LFS with genetic mutations that may be linked to earlier onset of severe cancers.

Since each generation also developed cancer at an earlier age, it is important to carefully monitor families across generations, Malkin said. The genetic instability primes them for progressively earlier cancers.

Li-Fraumeni Syndrome affects about one in 10,000 to 40,000 people and occurs when a child inherits one mutated copy of the p53 tumour suppressor gene from a parent, researchers said.

The discovery is importantand will helpscientists understand the causes of cancer in some families, said Dr. Barbara Whylie, CEO of the Canadian Cancer Society, which funded the research, along with the SickKids Foundation.