Clear-cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer – but not all cases are alike. A new Brady study has shown that there are notable differences in patients based on ancestry – and beyond this, there are distinct molecular subtypes that could affect the course of the disease and response to treatment.

In their study, published in Cancer Research Communications, Brady investigators com­pared molecular features of kidney tumors from carefully matched Black and White patients – 60 total – who underwent surgery for ccRCC. Using whole-exome sequencing and other advanced genetic techniques to look at gene mutations, and RNA sequencing to analyze gene activity, “we explored differ­ences associated with African and European genetic ancestry,” says medical oncologist Roy Elias, M.D., the study’s first author.

Among the genetic alterations they looked for were mutations in VHL, the von Hippel-Lindau tumor suppressor gene, which helps maintain the normal functions of cells. “We found that VHL mutations were less common in individuals of African descent, compared to those of European descent,” says the study’s senior author, Nirmish Singla, M.D., M.Sc. “Additionally, tumors from patients of European descent showed higher activity in pathways linked to inflammation, cell growth, and metabolism.” However, when the investigators examined the tumors at the molecular level, “we found that molecular categories explained the dif­ferences better than genetic ancestry alone.”

“Our findings suggest that using molecular subtypes could improve the precision and effectiveness of therapies,” says Elias. “Overall, this study emphasizes the impor­tance of representing a broad range of patient populations in cancer research and highlights how molecular classification can lead to better, more targeted treatments for all kidney cancer patients.” This work was generously supported by the Dan Hagaman Research Fund.