Comprehensive Molecular Characterization and Response to Therapy in Fumarate Hydratase–Deficient Renal Cell Carcinoma

Abstract

Although most FH-RCC tumors are due to germline <i>FH</i> alterations, a significant portion result from biallelic somatic <i>FH</i> loss. Both somatic and germline FH-RCC have similar molecular characteristics, with NF2 mutations, low tumor mutational burden, and high fraction of genome altered. Although immunotherapy alone produced no objective responses, combination mTOR/VEGF therapy showed encouraging results.