A new study suggest major cancer genes play a bigger role than thought in childhood cancer, potentially influencing surveillance, genetic testing, and treatment.

A new study suggest major cancer genes play a bigger role than thought in childhood cancer, potentially influencing surveillance, genetic testing, and treatment.


Childhood cancers more likely to come from major cancer genes than scientists thought

What causes cancer in kids? Genes have always been eyed as a key culprit, and now, the most comprehensive genetic survey to date suggests that major cancer genes are more common in affected children than thought. The analysis also reveals, to scientists’ surprise, that several children had problem genes tied to adult cancers like breast and ovarian cancer. The work may help doctors better screen for—and treat—cancers in young people, and identify other family members who might be at risk.

The researchers, at St. Jude Children’s Research Hospital in Memphis, Tennessee, and Washington University in St. Louis in Missouri, and led by pediatric researcher and St. Jude’s CEO James Downing, hunted for dangerous genes in 1120 cancer patients under the age of 20. They looked for mutations in healthy tissue, and focused on 60 genes known to be a major cause of at least some forms of the disease. Many children didn’t carry mutated versions of those genes—but more than expected did. DNA sequencing revealed that 95 kids—or 8.5%—had a copy of a gene that was either definitely or probably dangerous. That’s compared with, at most, the 5% the scientists thought they might see.

In some respects, that 8.5% is only part of what’s eye-catching. Some of these genes are big cancer drivers in adults yet haven’t historically been tied to childhood disease. For example, eight children with leukemia or other cancers had mutations in genes that dramatically raise risk of breast and ovarian cancer in adults—the BRCA genes and PALB2. It’s not clear whether those genes were also causing cancer in these children, although the scientists suspect they’re playing a role, they report today in The New England Journal of Medicine.

“We don’t today understand” all of this, says John Maris, a pediatric oncologist at the Children’s Hospital of Philadelphia in Pennsylvania. “If a child happens to have a breast cancer gene mutation, does that mean they’re at risk for breast cancer later in life, or is that contributing to the child’s cancer?”

Another big question mark is how family history connects to the mutated genes. Downing and his co-authors were struck that for patients whose family history information they could find, fewer than half had a family history of cancer. One explanation is that some mutations arose spontaneously during development and aren’t shared by the child’s relatives. Another is that the relevant information is missing, as pediatric oncologists often don’t ask about adult cancers in a family to better understand their young patients.

That’s something that might change. “Family history now matters more than ever,” says Stephen Chanock, a pediatric oncologist and head of the division of cancer epidemiology and genetics at the National Cancer Institute in Rockville, Maryland. “There may be a wider spectrum of cancers that are associated” with some of these genes than we thought.

Many pediatric oncologists think that in the near-term future, every child with cancer will have their genome sequenced—something that’s starting to happen in research settings. Identifying an array of cancer genes in sick children could serve many purposes. It might help guide treatment, if specific DNA affects how kids respond to certain drugs; it might alert doctors to children at risk for other cancers later in life, like breast cancer; and it might pinpoint families that could benefit from genetic counseling.

“Certainly not one out of 10 children are getting genetic testing or genetic counseling today,” says Maris, who studies the genetics of the childhood cancer neuroblastoma. “It is still very much the early days,” he adds, but the paper is “a very important blueprint for where the field needs to go.”