Team homes in on genetic causes of neuroblastoma

CHICAGO (Reuters) - A missing stretch of DNA on a chromosome involved in nervous system development may help explain why some children are predisposed to a deadly type of tumor called neuroblastoma, researchers reported on Wednesday.

The study is the first to show that repeats or deletions of a genetic sequence, as opposed to “spelling mistakes” in the four-letter genetic code -- influence cancer risk, said Dr. John Maris of the Children’s Hospital of Philadelphia, whose study appears in the journal Nature.

Hundreds of studies show that inherited genetic variations called single-nucleotide polymorphisms, or SNPs, play a role in the development of cancer. These are one-letter changes in the genetic code.

“This is the first paper to really show that copy number variation -- which is just another mechanism of evolution for why you and I are different -- can be involved in predisposition of cancer,” Maris said in a telephone interview.

Maris and colleagues also identified an entirely new gene -- neuroblastoma breakpoint family 23 or NBPF23 -- that plays a role in neuroblastoma. It is part of a family that was previously associated with the cancer, he said.

The research adds to a growing understanding of the genetic causes of neuroblastoma, a cancer affecting developing nerve tissue that accounts for 15 percent of all cancer deaths in children.

Last year, Maris identified three genes that affect the risk of aggressive neuroblastoma.

“Only two years ago, we had very little idea of what causes neuroblastoma,” Maris said in a statement. “Now we have unlocked a lot of the mystery of why neuroblastoma arises in some children and not others.”

His team scanned the genetic code of 846 white children with neuroblastoma and 803 seemingly healthy children. They found that children who were missing a stretch of genetic code on chromosome 1 -- which is especially important for nerve development -- are predisposed to develop the cancer.

“What our paper shows is that if you have copy number variations on chromosome 1, you are more likely to develop neuroblastoma,” Maris said.

Maris suspects copy number variation plays a role in how much of the NBPF23 gene is produced.

“It will take future study to understand whether or not it leads to a more aggressive or less aggressive form of the disease,” he said.

Maris suspects copy number variation will be found to play a role in other cancers. He hopes the findings will lead to more targeted treatments for neuroblastoma.

Editing by Maggie Fox and Mohammad Zargham