Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets.

ABSTRACT: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare yet highly lethal kidney cancer. To deepen our understanding of FH-deficient RCC, we conduct a comprehensive integrated genomic study. We analyze the association of FH alteration patterns with tumor heterogeneity and develop a CpG site-specific methylation signature for precise identification of FH-deficient RCC. Transcriptomic analysis unveils three distinctive molecular subtypes characterized by enrichment of immune/Angiogenic/Stromal (C1), WNT/Notch/MAPK (C2), and proliferation/stemness (C3) pathways, respectively. Tumors in C1 derive the most substantial survival benefit from a combination of immune checkpoint blockade (ICB) and anti-angiogenic therapy. Tumors in C2 display moderate response to this therapeu

SUBMITTER: Zhang X 

PROVIDER: S-EPMC12069531 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature