Pediatric Lymphoma Joins Family of BRCA2 Cancers

Helen Leask

July 26, 2019

For the first time, a pediatric cancer has been added to the "BRCA2 family."

Researchers at St. Jude Children's Research Hospital in Memphis, Tennessee, revealed that BRCA2 mutations were five times more common in children with non-Hodgkin lymphoma compared to a control group.

The study was published online on July 25 in JAMA Oncology.

Although this may seem like bad news, in fact it provides medicine with an unprecedented opportunity to head adult cancers off at the pass, according to study author Zhaoming Wang, PhD.

Identifying BRCA2 mutations early could give a head start to healthcare professionals whose job it is to follow these young patients into adulthood, he added.

Genetic counseling and BRCA2 testing of all survivors of childhood non-Hodgkin lymphoma is crucial, Wang said, especially in cases in which there is a family history of cancers suggesting BRCA2 involvement.

"There is a high chance [the patient] will test positive," he said. "Survivors whose test results are positive for these mutations can be offered surveillance for BRCA2-associated cancers, such as breast cancer and ovarian cancer, and consults for risk-reduction strategies."

For their study, Wang and colleagues used whole-genome sequencing for 1380 survivors of pediatric or adolescent lymphoma treated at St. Jude Hospital and compared the results to those for cancer-free adults in the Genome Aggregation Database. They found that BRCA2 mutations were five times more common in the childhood survivors of non-Hodgkin lymphoma.

Wang said, "In the general population, you might expect to see [a BRCA2 frequency of] 1 in 1000. We saw a fivefold increase, so this really is a telling enrichment of the mutation compared to the controls."

Although non-Hodgkin lymphoma runs in families, this is the first time that researchers have put a name to a genetic mutation associated with the disease.

"I was excited to see this," Wang told Medscape Medical News. "To the best of my knowledge, BRCA2 seems to be the first predisposition gene identified for non-Hodgkin lymphoma, and it may explain the familial non-Hodgkin lymphoma we observed [in the patient's families]."

Wang stressed that healthcare professionals need to be aware that BRCA2 cancers now include childhood non-Hodgkin lymphoma. "We're basically adding one new member into the BRCA2-associated cancers, along with breast, ovarian, prostate, pancreatic, and melanoma," he said.

As well as the implications for better surveillance, Wang said that BRCA2 testing during or after pediatric non-Hodgkin lymphoma could open the door to personalized approaches to treatment.

"I'm just speculating," he said, "but if BRCA2 is really a gene important for development of lymphoma, PARP [poly (ADP-ribose) polymerase] inhibitors could be one of the [treatment] options. And, more importantly, when these survivors grow up into adults and develop some other adult cancer, treatment can be tailored, and PARP inhibitors would certainly be a choice."

Wang acknowledged that the study shows an association, not causality. His team is currently investigating the genetic alterations in tumor samples from non-Hodgkin lymphoma survivors. "We need to understand how pathogenic BRCA2 mutations lead to lymphoma development," he said.

The study was funded by a grant to St. Jude Children's Research Hospital from the American Lebanese Syrian Associated Charities and by grants to St. Jude Children's Research Hospital from the National Institutes of Health. Wang and coauthors have disclosed no relevant financial relationships.

JAMA Oncol. Published online July 25, 2019. Full text

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