UVA Researchers: Children’s Cancer Test May Produce False Positives
Researchers at the University of Virginia have discovered a test used to detect a rare type of cancer in children may produce false positives. Their findings show a fusion of genes thought to be unique to the cancer also occurs during normal cell development.
Researchers in the UVA School of Medicine say many diagnostic measures are based on the idea that finding a particular fusion means detecting a specific cancer. They stress their discovery shows that process is not so clear cut.
The research team says doctors have been diagnosing young patients with alveolar rhabdomyosarcoma - or a muscle tumor that occurs most commonly in teens - based on a specific fusion of genes. But they have now found that same fusion occurring naturally in cells.
The scientists say the process only lasts for a short time during normal cell development, but it could result in a false positive for cancer.
"We need to understand that the fusions now are not so black and white - not 100% specific for cancer - and one thing we like to say is cancer is smart, but not original," said associate professor Hui Li.
Researchers also explain their work shows this fusion happening at an RNA level, when it has previously been thought to take place at the DNA level. The scientists want to do more testing to see if their finding is a general phenomenon that applies to other types of cancer.
They hope their research will eventually help doctors develop more accurate testing methods. University of Virginia Press Release
A test used to detect a type of cancer in children may produce false positives because it is based on a faulty assumption, researchers at the University of Virginia School of Medicine have determined.
The test works by detecting a gene fusion thought to be unique to a rare form of cancer known as alveolar rhabdomyosarcoma, but the new UVA research shows that the fusion actually occurs during normal cellular development as well. The fusion of genes lasts only a brief time during normal development, but a diagnostic test could potentially detect it and indicate the presence of cancer where this is none, the researchers believe.
"Cancer does express this fusion. But it's not totally unique now. It's not black and white now. It's shades of gray," said researcher Hui Li, PhD, of the School of Medicine's Department of Pathology and the UVA Cancer Center. "In normal development, it's only briefly expressed, so if we can understand the normal process a little better and know when exactly in development you see this, maybe we can develop a better assay to rule out this particular potential for false positives."
The findings serve as a word of caution for doctors evaluating children for alveolar rhabdomyosarcoma, a type of cancer of the muscle tissue that occurs most commonly among teenagers. While the new findings raise the possibility that a test could possibly detect a false positive, the test continues to have value, as doctors have multiple methods they can use to diagnose and confirm the presence of rhabdomyosarcoma.
Li and his team of researchers suspected the gene fusion might occur during normal muscle development but knew that they faced a challenge in demonstrating that was the case. "The general belief that we had in the lab is that cancer doesn't usually have something totally unique. It doesn't come up with something totally new – it highjacks a normal process," Li said.
But how were they to find a gene fusion that might exist only fleetingly, if it occurred at all? "Unless you look at the right cell at the right time, you never find these sort of things," Li said. "Without knowing when, we started from stem cells and just harvested time points along the muscle differentiation process. And lo and behold, we see the same fusion that everyone thinks is unique in this particular children's muscle tumor also shows up during muscle cell formation."
The research findings have been published by Cancer Discovery, a journal of the American Association for Cancer Research. The paper was authored by Huiling Yuan, formerly of UVA and now of Dongguan People's Hospital in Dongguan in China's Guangdong province; Fujun Qin, Mercedeh Movassagh, Hong Park, Wendy Golden, Zhongqiu Xie and Peng Zhang, all of UVA's Department of Pathology; Jeffrey Sklar of Yale; and Li.
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