Susanna Fletcher Greer, Chief Scientific Officer of the V Foundation, shared a post on LinkedIn:
“Translocation renal cell carcinoma, or tRCC, is an aggressive form of kidney cancer that is often misdiagnosed because it looks very similar to other kidney cancers under the microscope. And unlike many cancers, it does not carry the usual DNA changes that standard blood tests look for. That means the tools we rely on for liquid biopsy often miss it.
Remember that we can think about our DNA as a blueprint. Interestingly, most liquid biopsies work by trying to find typos in the plans themselves. But in tRCC, the problem is not the words: it’s the architect. In this cancer, a gene fusion creates a new, powerful protein that rewrites the instructions for how the building is built. Entire sections of the blueprint are rearranged. The building’s (AKA your DNA) original design is still there, but the new architect is forcing it to be built in a way it was never intended to be.
A new study from the V Foundation grantee Dr. Srinivas Viswanathan and lab Dana-Farber Cancer Institute takes a different approach. Instead of looking for changes in the DNA sequence, Dr. Viswanathan’s team looked for changes in how the cancer is using the DNA.
Since we know this about tRCC, the question then becomes: can we detect those altered instructions in a blood sample?
Using a method that reads chemical signals attached to DNA fragments circulating in the bloodstream, Dr. Viswanathan identified a distinct ‘activity pattern’ created by the TFE3 fusion that drives this cancer. Turns out that pattern could distinguish tRCC from other kidney cancers and from people without cancer, even when the amount of tumor DNA in the blood was extremely low.
Even more important, the signal rose and fell with the patient’s disease. In some cases, it increased months before scans showed the cancer was growing.
This finding is pivotal because accurate diagnosis is critical for tRCC. This cancer behaves differently and often responds differently to treatment than more common kidney cancers. When it is misclassified, patients may receive therapies that are less effective or be enrolled in the wrong clinical trials.
Bottom line: a simple blood test that can correctly identify and monitor this cancer could help guide treatment decisions earlier, detect recurrence sooner, and match patients to the therapies and trials most likely to help them.
Many cancers do not carry obvious DNA mutations but are driven by changes in gene activity. This work shows that instead of looking only for genetic ‘mistakes,’ we can learn a great deal by reading the cancer’s behavior. It is a shift from asking ‘what the DNA says in its blueprint’ to asking ‘what is the cancer actually doing?’.
And for patients with rare or hard to detect cancers, that shift could make all the difference.
Find the Viswanathan lab at Home | Viswanathan Lab at Dana-Farber Cancer Institute.”
More posts featuring Susanna Fletcher Greer on OncoDaily.