Children with Down syndrome are about 20 times more likely to develop acute lymphoblastic leukemia (ALL) than other children. To better understand this predisposition for cancer, a team of researchers from Baylor College of Medicine, Emory University and St. Jude Children’s Research Hospital have been awarded a grant from the Gabriella Miller Kids First Pediatric Research Program (Kids First) to sequence the genomes of more than 2,000 individuals with Down syndrome.
Dr. Philip Lupo and Dr. Karen Rabin, both associate professors of pediatric hematology-oncology at Baylor and Texas Children’s Cancer and Hematology Centers, are co-principal investigators of the study.
“This grant is unique in that it is supporting whole genome sequencing of individuals with Down syndrome to investigate why these children are more likely to develop congenital heart disease (CHD), other structural birth defects and leukemia when compared to those without Down syndrome,” Lupo said. “Two percent of children with Down syndrome will develop ALL and about 50 percent have congenital heart disease. We want to fully characterize why these children have an increased risk for these conditions.”
“While we know that children with Down syndrome have an extra copy of chromosome 21, we don’t fully understand what about chromosome 21 leads to an increased risk of CHD and ALL,” Rabin said. “This is an exciting prospect that could provide a greater understanding of which children will develop these conditions and why. We hope to improve how we predict risk of ALL and develop better treatments.”
The project will focus primarily on genes that the individual is born with (inherited DNA), but it also will include sequencing of leukemia samples (tumor DNA) from the same individuals to identify the genetic changes that are acquired by cells as they develop into leukemia after birth.
“This will allow us to compare what we see in inherited genetic code versus what is present in the tumor. The scale of these data is phenomenal,” Lupo said. “As a research community, we’ve done as much as we can with the technology that we have, so this project will provide an expanded pool of information and data for scientists to mine and re-examine for new evidence and insights.”
The Kids First program is a project of the National Institutes of Health, which supports whole genome sequencing studies focused on pediatric cancer or structural birth defects, and the resulting data will be made widely available to researchers as a resource.
Lupo and Rabin are collaborating with co-principal investigators Dr. Stephanie Sherman at Emory and Dr. Jun Yang at St. Jude. The sequencing will be completed by the Broad Institute of MIT and Harvard, utilizing samples from the Children’s Oncology Group and from a large multicenter study of CHD led by Dr. Sherman.
Lupo and Rabin are members of the NCI-designated Dan L Duncan Comprehensive Cancer Center at Baylor.