A new comprehensive analysis of thyroid cancer from The Cancer Genome Atlas Research Network has identified markers of aggressive tumors, which could allow for better targeting of appropriate treatments to individual patients. The finding suggests the potential to reclassify the disease based on genetic markers and moves thyroid cancer into a position to benefit more from precision medicine.
In this TCGA study, published recently in Cell, the researchers analyzed nearly 500 thyroid cancer samples to identify all genetic mutations that play a role. They found several new cancer genes as well as new variations of existing genes. They looked at the signaling pathways involved to understand what drives thyroid tumors. This approach helped them understand the genetic drivers of more of these cancers, reducing the percentage of “dark matter” cases—those with unknown genetic drivers – from 25 percent to 3.5 percent.
Those drivers can be broken down into two primary oncogenic groups: BRAF plus similar mutations and RAS plus similar mutations. But within these two primary groups, especially the BRAF group, several different subtypes of thyroid cancer exist.
“This study integrated a wide variety of genomic data to not only identify cancer drivers, but to compare how these different drivers behave,” says project co-lead for TCGA thyroid cancer analysis Gad Getz, PhD. “Interestingly, we found that subsets of BRAF-mutated thyroid cancers are driving cancer through distinct mechanisms, and that some of these subsets are associated with higher risk and less differentiated cancers.”
The researchers used this understanding to create measures or scores that can determine how a tumor signals and how aggressive a thyroid tumor is. These scores are being tested in a clinical trial to assess if the approach can lead to more targeted treatment recommendations. Read the study.
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