Another Gene Linked

Researchers at Children’s Cancer Institute have uncovered, for the first time, another gene linked to the cause of one of the most aggressive forms of childhood cancer – that could provide new targets for cancer therapy and change the way we treat the disease.

The Institute’s work shows that noncoding or ‘junk’ DNA can cause childhood cancer and contributes to the malignant nature of neuroblastoma – the most common solid cancer found in infants and young children that often presents as an aggressive, incurable disease.

The study, published in the prestigious US Journal of the National Cancer Institute, was led by Dr Tao Liu, Group Leader for Histone Modification at Children’s Cancer Institute and his colleague Professor Glenn Marshall, Head of Molecular Carcinogenesis Program at Children’s Cancer Institute, Director of the Kids’ Cancer Alliance and Director of the Kids’ Cancer Centre at Sydney Children’s Hospital.

It has been known for some time that the aggressive nature of neuroblastoma is often driven by a cancer-causing gene called MYCN. Each neuroblastoma cell carries many copies of MYCN, but the results of Dr Liu’s study reveal that DNA containing MYCN also contains ‘passenger DNA’, which dramatically adjusts the levels of MYCN in neuroblastoma cells and further fuels the cancer.

By uncovering a new long noncoding RNA (a type of RNA molecule) that plays a critical part in neuroblastoma tumor formation, Dr Liu’s research suggests that noncoding DNA is in fact not ‘junk’ at all. It actually plays a major role in regulating the levels of genes – including cancer-causing genes.

“I attended a conference a few years ago where it was suggested that long noncoding RNAs may also affect the occurrence of cancer,” says Dr Liu. “When I returned to the lab, I decided to study this further.

“I started researching one particular long noncoding RNA that didn’t yet have a name – as it had never been studied before. We called it lncUSMycN.”

Dr Liu’s team discovered that when lncUSMycN was blocked in neuroblastoma cells growing in the laboratory, the MYCN oncogene was ‘switched off’ by almost 90 per cent. Moreover, a study of large neuroblastoma tumors showed a direct link between poor survival rates and a higher level of lncUSMycN, independent of MYCN.

This is the first time it has been discovered that a long noncoding RNA can impact the progression of neuroblastoma, revealing that MYCN is not the only gene that contributes to the disease.

“Dr Liu’s study has improved our understanding of what leads to the development of neuroblastoma, and uncovered another potential target for this rare but devastating disease,” says Children’s Cancer Institute’s Head of Translational Research, Prof Glenn Marshall AM.

“Side-effects associated with conventional chemotherapy used to treat kids with cancer are a significant clinical problem. Research results such as these will help us discover new treatments, specifically designed for children, to ensure they experience the highest possible quality of life – and support further work to uncover other junk DNA targets for cancer therapy.”

Media enquiries: Catherine Arnott, Media & Communications Advisor; 02 9385 8879; carnott@ccia.org.au

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