Retinoblastoma is rare, affecting about one in 20,000 children. In Canada, about 25 children under age five are diagnosed each year with the tumour of the retina, the light-sensitive tissue at the back of the eye that detects light and colour.
For years, it was thought that the rapidly growing cancer was always caused by a mutation in a single gene, called the RB1 gene.
Now researchers at Toronto's Hospital for Sick Children and international collaborators have determined there is another type of the disease caused by a different gene — a cancer gene — which will change how doctors treat patients with this form of tumour.
"Everyone in the world thought retinoblastoma was one cancer that was initiated by the retinoblastoma gene —only one kind of cancer, although there are two forms," said principal researcher Dr. Brenda Gallie, a world-renowned expert in the disease.
Both these forms result from the deletion of RB1, a tumour suppressor gene whose job it is to regulate cell growth and keep cells from dividing too rapidly or in an uncontrolled way.
In about 60 per cent of cases, the RB1 gene is missing from cells in the retina, and patients are not at risk of passing the disease to their offspring.
But for the remaining children, the genetic mutation is present in all the cells of their body. Usually, the mutation arises spontaneously around the time of conception, but in 10 per cent of cases, the mutated gene is inherited from a parent.
These youngsters often develop tumours in both eyes. And although retinoblastoma has a high cure rate in developed countries like Canada, survivors have an elevated risk of developing another form of cancer later in life, Gallie said.
"If you carry only one normal copy of the retinoblastoma gene, you're at lifelong risk at a much higher rate than the general population to get other cancers," said Gallie, citing the case of musician Jeff Healey, who lost both his eyes to retinoblastoma as a baby and died five years ago at age 41 of a second cancer.
"But this new form doesn't carry that," she said. "It's just the eye, it's just that tumour."
The research, published in the journal Lancet Oncology, should be heartening for patients who turn out to have this subgroup of retinal tumour and for their families.
"The important thing is that without this new discovery, we would have been telling them that their child was at significant risk to get cancer in the other eye, their next generation would be at a 50 per cent risk for (retinal) cancer, and they'd be at risk for their life for other cancers," Gallie said.
"Now we can tell them they're at zero risk (following treatment). They're normal. That's a huge impact."
Finding out that his retinoblastoma was not caused by the RB1 deletion was a huge relief for Dr. Aleks Meret, a pediatric resident at Queen's University.
Toronto-born Meret was diagnosed with retinoblastoma at three months old. He had his right eye removed and was fitted with an artificial eye.
While the treatment stopped the cancer from spreading to his brain or elsewhere in his body, Meret had since lived with the belief that he had a higher risk for another cancer somewhere in his future.
"When I was in medical school, I realized what that meant, developing new cancers and being worried about that," he said Tuesday from Kingston, Ont. "And certainly the hereditary part as well, for having some kids in the future and the implications that that would have.
"It's nice to know that you don't have those risks."
Dr. Linn Murphree, director of the retinoblastoma program at the Children's Hospital Los Angeles, said the researchers have "done a beautiful job of defining a very important subgroup of retinoblastoma patients."
"And it points out again the importance of the exception to prove the rule, to understand the exact cellular mechanism that cancer can use to get established," said Murphree, whose team was instrumental in identifying the RB gene.
Murphree said this subgroup of tumour is typically diagnosed earlier, is large and more rapidly developing than other retinoblastomas, which means doctors will treat them more aggressively — likely opting to remove the affected eye rather than trying to salvage it and potentially jeopardizing the child's life.
"We always take our clues for aggressiveness of treatment based on the perceived risk that the tumours present to the child and the family," he said from Los Angeles.
Murphree said the research underscores the importance of genetic testing, especially when the cancer is found in only one eye, because the tumour's genetic underpinnings will affect how doctors treat and follow-up on the child over time.
"I do think this field owes these authors a particular debt of gratitude for their persistence in ... differentiating the different kinds of retinoblastomas," he said.
"Dr. Gallie has played a major role in virtually all the steps so far in understanding this disease. And this is another one."