Lina Posada Calderon, MD, provides insights on germline BAP1–associated renal cell carcinoma

In an interview at the 2026 Desai Sethi Urology Institute Urology on the Beach meeting, Lina Posada Calderon, MD, discussed the background and key takeaways from her team’s study examining renal cell carcinoma (RCC) associated with germline BAP1 tumor predisposition syndrome, one of the most recently characterized hereditary RCC syndromes. Calderon is a sixth-year resident at Weill Cornell Medicine in New York, New York.

According to Calderon, BAP1-associated disease has been minimally described in the literature due to its rarity, with existing knowledge largely limited to isolated case reports. Drawing on a cohort of patients treated at Memorial Sloan Kettering Cancer Center, the investigators sought to better define the clinical behavior of this disease and begin informing evidence-based treatment recommendations.

Overall, the results indicated that BAP1-associated RCC differs from sporadic RCC both clinically and biologically. While approximately 70% of germline BAP1-associated tumors are clear cell RCC—similar to sporadic disease—a notable proportion present with other histologic subtypes. Clinically, the disease demonstrates a wide spectrum of behavior; some patients develop highly aggressive tumors, while others experience recurrent, indolent, low-grade disease without progression to aggressive cancer. This variability stands in contrast to sporadic RCC, which are typically associated with more aggressive clinical courses.

From a biological perspective, Calderon highlights fundamental differences in tumor evolution between germline and sporadic disease. In sporadic clear cell RCC, BAP1 mutations usually arise later as subclonal events following VHL loss, often driving aggressive behavior. In contrast, germline BAP1-associated tumors harbor the mutation from tumor initiation, potentially altering tumor development from the outset. The study also raises intriguing hypotheses regarding chromosome 3p loss and allele-specific effects in germline disease, underscoring how inherited BAP1 mutations may shape tumor behavior in ways distinct from sporadic RCC and pointing toward important areas for future research.