New gene variants increase risk of paediatric cancer

October 4, 2012
New gene variants increase risk of paediatric cancer
Credit: Shutterstock

Two new gene variants have been discovered by researchers from Italy and the United States that increase the risk of neuroblastoma, a paediatric cancer. This discovery was made using automated technology to perform genome-wide association studies (GWAS) on DNA from thousands of subjects. The study has effectively broadened our understanding of how gene changes may make a child susceptible to this early childhood cancer, as well as causing a tumour to progress.

Neuroblastoma is a long-term debilitating and life-threatening disease that is associated with poor long-term survival and affects approximately 0.18 in 10,000 people in the European Union, the equivalent of around 9,100 people. It is the most common solid tumour outside the brain in children; symptoms may include weakness, bone pain, loss of appetite and fever. In many cases it is present at birth but is diagnosed later when the cancer has spread to other parts of the body and the child begins to show symptoms of the disease.

'We discovered common variants in the HACE1 and LIN28B genes that increase the risk of developing neuroblastoma. For LIN28B, these variants also appear to contribute to the tumour's progression once it forms,' said lead author Sharon J. Diskin, Ph.D., a paediatric cancer researcher at The Children's Hospital of Philadelphia. 'HACE1 and LIN28B are both known cancer-related genes, but this is the first study to link them to neuroblastoma.'

Diskin and colleagues, including senior author John M. Maris, M.D., director of the Center for Research at Children's Hospital, published the study online in . Neuroblastoma strikes the and usually appears as a solid tumour in the chest or abdomen. It accounts for 7 % of all childhood cancers, and 10 to 15 % of all childhood cancer deaths.

The research team performed a GWAS, and compared DNA from 2,800 neuroblastoma patients with that of nearly 7,500 healthy children. They found two common gene variants associated with neuroblastoma, both in the 6q16 region of chromosome 6. One variant is within the HACE1 gene, the other in the LIN28B gene. They exert opposite effects: HACE1 functions as a suppressor gene, hindering cancer, while LIN28B is an oncogene, driving cancer development.

The study showed that low expression of HACE1 and high expression of LIN28B correlated with worse patient survival. To further investigate the gene's role, the researchers used genetic tools to decrease LIN28B's activity, and showed that this inhibited the growth of neuroblastoma cells in culture.

The new research builds on previous work and GWAS work by Children's Hospital investigators implicating other common gene variants as neuroblastoma oncogenes. As in the current study, these gene variants show a double-barreled effect, both initiating cancer and provoking its progression.

'In addition to broadening our understanding of the heritable component of neuroblastoma susceptibility, we think this research may suggest new therapies,' Diskin added. 'Our follow-up studies will focus on how we may intervene on these genes' biological pathways to develop more effective treatments.'

Currently in the EU, several medicines exist and are authorised for the treatment of neuroblastoma. Treatments for neuroblastoma include surgery, chemotherapy (medicines to treat ) and radiotherapy (treatment with radiation).

Explore further: New gene variants raise risk of neuroblastoma, influence tumor progression

More information: Diskin, S.J., et al. 'Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma', Nature Genetics, 2012. doi: 10.1038/ng.2387

Related Stories

New gene variants raise risk of neuroblastoma, influence tumor progression

September 4, 2012
Researchers have discovered two gene variants that raise the risk of the pediatric cancer neuroblastoma. Using automated technology to perform genome-wide association studies on DNA from thousands of subjects, the study broadens ...

Recommended for you

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

Scientists identify key regulator of male fertility

September 19, 2017
When it comes to male reproductive fertility, timing is everything. Now scientists are finding new details on how disruption of this timing may contribute to male infertility or congenital illness.

New assay leads to step toward gene therapy for deaf patients

September 18, 2017
Scientists at Oregon State University have taken an important step toward gene therapy for deaf patients by developing a way to better study a large protein essential for hearing and finding a truncated version of it.

Genomic recycling: Ancestral genes take on new roles

September 18, 2017
One often hears about the multitude of genes we have in common with chimps, birds or other living creatures, but such comparisons are sometimes misleading. The shared percentage usually refers only to genes that encode instructions ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.