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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

Featured Little Hero: Ayven Trestick

Ayven began having strange symptoms back in April 2012 when she started vomiting randomly. It was shortly after we had introduced solid foods. After discussion with her pediatrician, we chalked it up to either a food aversion or gas bubbles. Shortly after, Ayven also began to have a swollen, hard belly. Again, after discussion with her doctor, we decided that it may have been caused by a food allergy or an intolerance. She tested negative for a few food allergies, so our next step was to eliminate dairy from her diet. After almost two months of no dairy, and no real change with her stomach issues, we approached the doctor about the possibility of Celiac Disease. Ayven’s symptoms were almost identical, and we were certain that we had finally figured out what was causing her problems. She was sent to our local hospital on Tuesday, December 11, 2012 (Ayven was 15 months old) to have routine blood work and an x-ray to confirm Celiac Disease. To our great surprise, and our worse possible fear, the x-ray raised some red flags and she was sent for an emergency ultrasound. The ultrasound confirmed that our nightmare had become a reality. It showed that she had a tumor the size of a large grapefruit in her abdomen. The tumor was inoperable because of its size, and the fact that it encased her aorta and many major vessels. Ayven was given the official diagnosis of stage III, intermediate risk, neuroblastoma.

She began treatment on 12/14/12. After four rounds of chemotherapy, we took her to MSKCC to discuss surgery with Dr. LaQuaglia. He decided that since Ayven was stage III, MYCN non-amplified, it may be a better option to observe her tumor instead of performing the risky surgery. 
Since Ayven’s tumor had been reacting so well to chemo, her doctors decided to go ahead with two more rounds, and eventually two more…a total of eight rounds of chemo. 
Ayven’s tumor still encases her aorta and many of the major vessels in her body.

We now are waiting to hear from Dr. L for his recommendations and also Dr. Maris (from CHOP).

We know that our little girl will beat this, and keep the faith!

You can follow Ayven’s updates on facebook: www.facebook.com/SavinAyven

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