FH
Overview
FH (Fumarate Hydratase) encodes a mitochondrial and cytosolic enzyme catalyzing fumarate-to-malate conversion in the TCA cycle. Germline FH mutations cause hereditary leiomyomatosis and renal cell cancer (HLRCC), predisposing to aggressive type 2 papillary RCC. In non-clear cell RCC profiling, FH is referenced as a known germline predisposition gene.
Alterations observed in the corpus
- Referenced as a known germline kidney cancer predisposition gene in the context of comprehensive somatic profiling of 167 non-clear cell RCCs; not significantly mutated somatically in this cohort PMID:25401301.
- Defines FH-deficient uRCC subset; somatic homozygous deletion (T41) is a novel non-germline mechanism for FH-deficient RCC. FH-loss and 2SC IHC alone insufficient to distinguish HLRCC from sporadic FH-deficient RCC; genetic counselling required PMID:27713405
- Identified as an additional germline cancer-predisposition finding (<1%) in a 451-patient prospective prostate cancer cohort profiled with MSK-IMPACT; clinical significance noted as emerging PMID:28825054
Cancer types (linked)
- PRCC/CHRCC (non-clear cell RCC): FH is a germline predisposition gene for RCC; somatic FH mutations not recurrently detected in this cohort PMID:25401301.
Co-occurrence and mutual exclusivity
- No co-occurrence or mutual exclusivity data reported in the corpus.
Therapeutic relevance
- No direct therapeutic associations reported for somatic FH in the corpus.
Open questions
- The role of somatic versus germline FH alterations in sporadic non-clear cell RCC subtypes requires further characterization.
Sources
This page was processed by entity-page-writer on 2026-05-11. - PMID:27713405
This page was processed by entity-page-writer on 2026-05-15. - PMID:28825054
This page was processed by wiki-cli on 2026-05-15.