Researchers have found a possible source of the variability in patterns of clear cell renal cell carcinoma (RCC), the most common kidney cancer diagnosed in adults. Katherine Alexander, PhD, Assistant Professor at Cold Spring Harbor Laboratory, and Shelley Berger, PhD, Professor at the University of Pennsylvania, have identified two different patterns of cellular structures known as nuclear speckles in renal cell tumors. Their research, published in Nature Cell Biology, shows a potential correlation between speckle patterns and patient outcomes.
“We found that different therapies are more or less effective depending on how the speckles look. This means potentially if a patient comes in with a normal or aberrant speckle state, they might be more responsive to one drug or another. Of course, more research needs to be done," said Dr. Alexander.
Discovered over 100 years ago, nuclear speckles are tiny cellular structures that reside in the nucleus. Here, they’re thought to intermingle with DNA and help regulate gene activity. Dr. Alexander’s research reveals that nuclear speckles have two different signatures in clear cell RCC: normal-like and aberrant. Normal-like speckles tend to congregate toward the center of the nucleus. Aberrant speckles are more dispersed.
“How these signatures affect patient outcomes remains a mystery for now,” Dr. Berger said. “However, the search for answers may lead to more personalized treatments. This discovery offers a new starting point in clear cell RCC.”
“It’s the first suggestion that this would be potentially applicable to giving someone [diagnosed with clear cell RCC] one drug or another. To be able to tell a patient, ‘Your tumor looks like this, so we think this drug will work better than this drug,’ is something we really need," Dr. Alexander added.
The team analyzed speckles in over 20 different types of cancers, from melanomas to breast cancer. However, only clear cel RCC showed a correlation between speckle patterns and patient outcomes. What makes this cancer special? Dr. Alexander’s findings point to HIF-2𝛼, a protein typically overactive in clear cell RCC. Further study is ongoing.
Disclosure: For full disclosure of all study authors, visit Nature Cell Biology.
