Philip Abbosh1, Srinath Sundararajan2, Sherri Z Millis3, Adam Hauben3, Sandeep Reddy3, Daniel M Geynisman4, Robert Uzzo1. 1. Division of Urological Oncology, Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. 2. Division of Hematology and Oncology, Department of Medicine, University of Arizona, Tuscon, AZ, USA. Electronic address: ssundararajan@email.arizona.edu. 3. Caris Life Sciences, Phoenix, AZ, USA. 4. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
Abstract
Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with no standard treatment. We performed molecular profiling of 12 chRCC cases to identify alterations predictive of response to therapy. Tests included immunohistochemistry assays, fluorescence in situ hybridization, and next-generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%) samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%) and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes were identified. In summary, molecular profiling of chRCC identified alterations in genes and protein expression that might provide a mechanistic rationale for off-label use of approved therapies in advanced chRCC, and could guide the design of molecularly targeted clinical trials. PATIENT SUMMARY: In this study, we evaluated samples of a rare type of kidney cancer (chromophobe type) and identified potential genetic markers that could be used to individualize treatment and possibly improve treatment outcomes.
Metastatic chromophobe renal cell cancer (chRCC) is a rare subtype of RCC with no standard treatment. We performed molecular profiling of 12 chRCC cases to identify alterations predictive of response to therapy. Tests included immunohistochemistry assays, fluorescence in situ hybridization, and next-generation sequencing. Analysis identified c-KIT overexpression in 6/9 (67%) samples analyzed, and loss of protein expression of RRM1 and MGMT in 11/12 (92%) and of PTEN in 7/12 samples (58%). Mutations of TP53, PTEN, APC, and VHL genes were identified. In summary, molecular profiling of chRCC identified alterations in genes and protein expression that might provide a mechanistic rationale for off-label use of approved therapies in advanced chRCC, and could guide the design of molecularly targeted clinical trials. PATIENT SUMMARY: In this study, we evaluated samples of a rare type of kidney cancer (chromophobe type) and identified potential genetic markers that could be used to individualize treatment and possibly improve treatment outcomes.