(Ivanhoe Newswire) -- Two new studies from The Children's Hospital of
Philadelphia advance the search for genetic events that result in
neuroblastoma, a puzzling, often deadly type of childhood cancer.
Originating in the peripheral nervous system, neuroblastoma is the most
common solid cancer of early childhood and causes 15 percent of all
childhood cancer deaths. "Only two years ago we had very little idea of what
causes neuroblastoma," study leader John M. Maris, M.D., chief of Oncology
and director of the Cancer Center at The Children's Hospital of Philadelphia
is quoted as saying. "Now we have unlocked a lot of the mystery of why
neuroblastoma arises in some children and not in others."
In the largest gene study to date in pediatric oncology, Maris's study team
performed a genome-wide association study to discover that common variants
in the gene BARD1 increase a child's susceptibility to a high-risk form of
neuroblastoma.
A second genome-wide study found that a copy number variation (CNV)—a
missing stretch of DNA—along a structurally weak location on chromosome 1
plays an important role in the development of neuroblastoma.
The researchers made use of highly automated gene-analyzing technology at
the Center for Applied Genomics at Children's Hospital of Philadelphia,
directed by Hakon Hakonarson, M.D., Ph.D., a co-author of both studies. They
used specimens collected from around the world through the Children's
Oncology Group.
The BARD1 gene had already attracted attention from oncology researchers
because it is associated with the gene BRCA1, which was the first discovered
familial breast cancer gene. "Researchers have suspected that variants in
BARD1 also increased the risk of breast cancer, but no one has found
compelling evidence of this," said Maris. "Instead, surprisingly, our
genome-wide association studies found that BARD1 is a susceptibility gene
for neuroblastoma, and perhaps other cancers as well."
Maris's second study, spearheaded by Dr. Sharon Diskin, also of The
Children's Hospital of Philadelphia, found that an inherited CNV located at
chromosome 1q21.1 is associated with neuroblastoma. The chromosome region
contains a large family of genes that are involved in the development of the
nervous system, and the CNV they discovered changes how much of one
particular gene is made within normal nerve and neuroblastoma cells.
As gene studies continue to better define the genetic landscape of
neuroblastoma, added Maris, pediatric oncologists can develop more precise
targeted treatments to improve survival and quality of life for children
with this complex disease.
SOURCE: Nature Genetics, May 3, 2009, and Nature, June 17, 2009
