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Researchers identify gene variants linked to a high-risk children's cancer

CHOP scientists report on genetic links to neuroblastoma

Children's Hospital of Philadelphia

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IMAGE: Hakon Hakonarson, MD, PhD, is director of the Center for Applied Genomics at Children's Hospital of Philadelphia. view more 

Credit: Children's Hospital of Philadelphia

Pediatric researchers in the Roberts Collaborative for Genetics and Individualized Medicine at Children's Hospital of Philadelphia have identified common gene variants that raise the risk of developing an aggressive form of the childhood cancer neuroblastoma. The discovery may assist doctors in better diagnosing subtypes of neuroblastoma.

Co-led by a genomics expert and a pediatric oncologist with expertise in neuroblastoma, the team from Children's Hospital of Philadelphia (CHOP) reported that common variants in the MMP20 gene are associated with deletions on chromosome 11q. "These inherited variants predispose to 11q deletions, which are a strong risk factor for an aggressive form of neuroblastoma," said co-study leader Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP.

The study appeared online Sept. 18 in Nature Communications.

"We already knew that 11q deletions are biomarkers that predict poor outcomes in neuroblastoma," said co-study leader John M. Maris, MD, a pediatric oncologist at CHOP's Center for Childhood Cancer Research. "This new research helps us to more precisely predict how a neuroblastoma tumor will behave, so it improves our diagnostic capabilities."

A cancer of the peripheral nervous system that usually occurs as a solid tumor in a child's chest or abdomen, neuroblastoma is the most common cancer in infants. It accounts for a disproportionate share of cancer deaths in children.

The CHOP researchers previously identified six other genetic risk variants for neuroblastoma over the past decade, so the current investigation offers new insights into the genetic architecture of this complex form of cancer.

In the current study, the team performed a genome-wide association study in 113 tumors from neuroblastoma patients harboring 11q deletions, compared to 5,100 ancestry-matched controls. The research yielded common variants in the MMP20 gene, located on chromosome 11q22.2. A replication study in 44 independent cases and 1,900 controls found similar results.

The authors added that further studies should investigate the mechanisms by which MMP20 variants give rise to neuroblastoma tumors.

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The National Institutes of Health supported this research (grants HG006830 and CA124709).

Xiao Chang, et al "Common variants in MMP20 at 11q22.2 predispose to 11q deletion and neuroblastoma risk," Nature Communications, published online Sept. 18, 2017. http://doi.org/10.1038/s41467-017-00408-8

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 546-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

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