Almost one in every 10 children with cancer was born with an inherited genetic mutation predisposing them to develop the disease, according to a joint study by Washington University and St. Jude Children’s Research Hospital in Memphis.
The research suggests that genetic screening could provide an important tool for diagnosing cancers earlier and avoiding ineffective treatments.
The research, published in the New England Journal of Medicine, is the latest finding in a five-year collaboration known as the St. Jude—Washington University Pediatric Cancer Genome Project. It's aimed at better understanding the genetics origins of childhood cancers.
Rick Wilson, who directs the McDonnell Genome Institute at the Washington University School of Medicine, said this phase of the work involved sequencing the genomes of more than a thousand cancer patients under the age of 20 to look for mutations known to be linked to cancer. The study focused on mutations the children were born with, rather than those they acquired from exposure to cancer-causing substances, like second-hand cigarette smoke.
“We found a higher number of inherited mutations than we expected,” Wilson said. In all, 8.5 percent of the young patients had mutations in genes that predisposed them to cancer. “Our number is probably a little low, because we’re looking at genes that we know are associated with cancer risk,” Wilson said. “There are probably other genes that also predispose you to cancer that we simply just don’t understand yet.”
The researchers also found that more than half of the children with inherited mutations lacked any family history of cancer. That may seem counterintuitive, but Wilson said it's not surprising. “A lot of people just don’t know their family history,” Wilson said. “So you can’t rely on that as an easy determiner of whether or not there’s a familial risk.”
Unlike self-reported cancer risk, which is unreliable, genome sequencing will reveal any known potentially cancer-causing mutations. “And that may, or may not, change the way that you approach that particular patient’s care,” Wilson said.
For example, for some patients, having a specific genetic mutation could mean that a particular approach to treating their disease will not work. “A lot of leukemia patients might benefit from a drug that turns off a mutation in a gene called FLT3,” Wilson said. “But if that same patient has a mutation in another gene, maybe TP53, that just basically makes that treatment useless.”
TP53 is among the most common inherited mutated genes in pediatric cancer.
Knowing a person’s genetic make-up from birth could also signal the need for earlier cancer screenings. “If we had a patient that was born with one bad copy of the APC gene, which is associated with hereditary colon cancer, that’s a patient that you might start colonoscopy screening much, much earlier than when we’re all told to start it at age 50,” Wilson said.
And earlier detection could mean the difference between surviving cancer and dying from it. “It’s almost a universal truth that if you catch cancer early, you have a much better chance of successfully treating it.”
Right now, whole genome sequencing is still expensive — Wilson puts the cost, including analysis, at about $10,000. He said St. Jude has raised the money for a clinical trial to sequence the genomes of all the children who come there for cancer treatment. “That’s sort of revolutionary,” Wilson said. “If you go to any other cancer center in the country, the chances that a new pediatric cancer patient has their genome analyzed in any way is probably pretty small. It’s just not done very many places.”
Wilson said a lot more work needs to be done before physicians — and insurance companies —will be convinced of the benefits of routine genetic screening. “We need to look at lots more kids, we need to do lots more analyses on the data that we do have. But it’s exciting,” Wilson said. “You can kind of see where it’s going to go in the future, and how it’s going to make a difference.”
The current study was supported by funding from the American Lebanese Syrian Associated Charities and a grant from the National Cancer Institute.
Follow Véronique LaCapra on Twitter: @KWMUScience
