A new study from the University of Michigan Health Rogel Cancer Center and the Department of Pathology has found a way to uncover hidden genetic changes in a type of kidney cancer that could open up new treatment options for patients.
The research, published in the journal Modern Pathology, focuses on a gene called TRIM63 and how it could help detect mutations that are often missed by standard testing.
Kidney cancer, also known as renal cell carcinoma, is one of the most common cancers worldwide. It starts when cells in the kidneys grow out of control, forming tumors.
One rare subtype is called microphthalmia-associated transcription factor renal cell carcinoma, or MiTF RCC for short.
This form of cancer tends to occur in younger patients and can be aggressive, meaning it spreads quickly if not caught early.
Doctors usually diagnose MiTF RCC using a special test called fluorescent in situ hybridization, or FISH.
This test looks for specific DNA changes in two genes known as TFE3 and TFEB, which are often rearranged in this type of cancer.
To perform the test, scientists use fluorescent probes that attach to certain chromosomes. Under a microscope, the probes light up, allowing doctors to see whether a genetic rearrangement has occurred. Because of its precision, the FISH test is considered the “gold standard” for diagnosing MiTF RCC.
However, the FISH test is not perfect. Sometimes, it fails to detect the mutation even when the cancer is present. These false-negative results can be a serious problem because they may prevent patients from receiving the most appropriate treatment or from joining clinical trials that could help them.
Dr. Rohit Mehra, a professor of pathology at the University of Michigan, noticed something unusual in his research. Some kidney cancer cases that tested negative for MiTF using the FISH test still showed suspicious signs when examined under the microscope.
Curious about what was happening, Mehra and his team decided to dig deeper into the genetics of these cases.
They discovered that many of these “negative” tumors had high levels of activity in a gene called TRIM63. This gene had already been recognized as a useful marker for MiTF RCC, but its connection to FISH-negative cases had not been studied before.
TRIM63 had been used as a clinical biomarker at the University of Michigan for over two years, helping doctors identify MiTF RCC. Still, no one had looked at whether TRIM63 could reveal hidden genetic changes when FISH results came back negative.
To test this idea, Mehra and his research team conducted additional genomic testing on kidney tumor samples. They found 20 cases where the tumors were TRIM63-positive but FISH-negative.
After deeper testing, they discovered that about 70% of those tumors actually did have MiTF gene rearrangements — meaning the FISH test had missed them. This finding shows that when a tumor is positive for TRIM63 but negative by FISH, further genetic testing can uncover hidden mutations that standard tests might overlook.
This discovery could be a big step forward in kidney cancer diagnosis. It means that patients who might otherwise be misdiagnosed or miss out on potential treatments could now receive more accurate and personalized care. Identifying MiTF RCC correctly is important because it can influence how doctors plan treatment and which clinical trials a patient may qualify for.
The study also highlights the importance of combining traditional pathology tools with modern genomic testing. By integrating these methods, doctors can get a clearer picture of what’s really happening inside a tumor. The researchers believe this approach could be applied to other cancers as well, where certain genetic mutations remain hidden despite standard testing.
In summary, this study shows that the TRIM63 gene may act as a key signal for hidden mutations in certain kidney cancers.
When doctors see suspicious tumors that test negative for MiTF RCC using the FISH test, checking for TRIM63 overexpression and performing additional genomic testing could make a major difference. It’s an example of how careful observation and advanced science can work together to improve diagnosis and treatment for patients.
Overall, this research not only advances our understanding of kidney cancer genetics but also emphasizes the need for better, more sensitive testing methods. By uncovering these hidden mutations, doctors can provide more accurate diagnoses, more effective treatments, and better outcomes for patients facing this challenging disease.
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The study is published in Modern Pathology.
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