Human dark brown eyes close-up.  Side look
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A discovery by surgeon and ocular oncologist Jesse Berry, MD, of Children’s Hospital Los Angeles (CHLA), has identified tumor DNA in the eye fluid of patients that can help identify and guide treatments of the presence of retinoblastoma, an eye cancer that occurs in infants and toddlers. New findings of this research were reported recently in Nature Communications. The discovery of what is essentially a liquid biopsy, will aid in much earlier diagnosis as the cancer occurs in the back of the eye and is not readily observable. Due to the difficulty of diagnosing this condition, retinoblastoma can lead to loss of vision, loss of one or both eyes, and even death.

Until now, the condition has been discovered by parents who notice a particular glow in their young child’s eye in low light, or from a flash photograph. As a result, children would be presumed to have retinoblastoma and subsequently treated without a definitive diagnosis. This changed in 2017 when Berry’s research found the ability to take the tumor DNA from fluid taken from the front of the eye, which is called aqueous humor. This allowed  doctors to generate a confirmed genetic diagnosis before surgical intervention, allowing for earlier and more defined diagnosis and treatment.

“As a clinician who treats these patients, I was so frustrated because I would see two kids who looked the same clinically and who received the same treatment,” said Berry. “One child would respond beautifully. But the other child had a more aggressive tumor that didn’t respond to treatment or reoccurred. I felt like there had to be something happening at the cellular level responsible for what we were seeing. We now know that molecular analysis of the aqueous humor can explain those differences.”

The majority of retinoblastoma tumors result from a mutation in the Rb gene, although also has been shown to occur due to epigenetic changes. One of the most significant epigenetic changes—called methylation—is caused by a chemical alteration to the gene that can change a normal cell into a tumor cell. For the recent research, Berry’s team set out to determine the methylation status in aqueous humor samples associated with retinoblastoma and were able to identify a methylation signature that identified aggressive tumors along with 294 genes that were regulated by methylation to encourage tumor growth.

“Reliable biomarkers are needed to guide treatment decisions for children with retinoblastoma,” said Liya Xu, PhD, principal investigator at CHLA and assistant professor at the Keck School of Medicine of USC. “By identifying more genes that play a role in this cancer and seeing how these genes behave, we are paving the way for a whole host of potential therapeutic targets. This brings us closer and closer to optimizing treatments so we can prevent blindness in these young patients.”

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