ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020
Targeted sequencing of FH-deficient uterine leiomyomas reveals biallelic inactivating somatic fumarase variants and allows characterization of missense variants.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
- Uterine leiomyomas in HLRCC: a scoping review of presentation, histopathology, treatment patterns, and reproductive implications.European journal of human genetics : EJHG · 2026Review
- Fumarate Hydratase-Deficient Uterine Leiomyomas: Germline Genetic Findings and Clinical Follow-Up in a Single-Center Cohort.Diagnostics (Basel, Switzerland) · 2026Article
- Review
- HIF-1α Signaling in Uterine Fibroids: A Central Integrator of Hypoxic, Hormonal, and Fibrotic Pathways.Oxygen (Basel, Switzerland) · 2026Article
- Fumarate hydratase-deficient uterine leiomyoma: A rare case report and literature review.Frontiers in oncology · 2026Article
- The epidemiology and pathogenesis of uterine fibroids.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025Review
- Diagnostic Value and Interobserver Reproducibility of Histopathological Features in Fumarate Hydratase-Deficient Uterine Leiomyomas.Diagnostics (Basel, Switzerland) · 2025Article
- Glycolytic Reprogramming in Uterine Fibroids: Genetic, Transcriptomic, Proteomic, and Metabolomic Insights.Genes · 2025Review
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Functional analysis ofGenetics in medicine open · 2025Article
- FH deficient uterine leiomyomas-a case series.Heliyon · 2024Article
- A View on Uterine Leiomyoma Genesis through the Prism of Genetic, Epigenetic and Cellular Heterogeneity.International journal of molecular sciences · 2023Review
- Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment.Endocrine reviews · 2022Review
- Epigenomic and enhancer dysregulation in uterine leiomyomas.Human reproduction update · 2022Review
- Fumarate hydratase variant prevalence and manifestations among individuals receiving germline testing.Cancer · 2022Article
- Prenatal phenotype of PNKP-related primary microcephaly associated with variants affecting both the FHA and phosphatase domain.European journal of human genetics : EJHG · 2022Article
- [FH-deficient renal cell carcinoma expands the spectrum of renal papillary tumors].Der Pathologe · 2021Review
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10 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Uterine leiomyomas (ULs) constitute a considerable health burden in the general female population. The fumarate hydratase (FH) deficient subtype is found in up to 1.6% and can occur in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome. We sequenced 13 FH deficient ULs from a previous immunohistochemical screen using a targeted panel and identified biallelic FH variants in all. In eight, we found an FH point mutation (two truncating, six missense) with evidence for loss of the second allele. Variant allele-frequencies in all cases with a point mutation pointed to somatic variants. Spatial clustering of the identified missense variants in the lyase domain indicated altered fumarase oligomerization with subsequent degradation as explanation for the observed FH deficiency. Biallelic FH deletions in five tumors confirm the importance of copy number loss as mutational mechanism. By curating all pathogenic FH variants and calculating their population frequency, we estimate a carrier frequency of up to 1/2,563. Comparing with the prevalence of FH deficient ULs, we conclude that most are sporadic and estimate 2.7-13.9% of females with an FH deficient UL to carry a germline FH variant. Further prospective tumor/normal sequencing studies are needed to develop a reliable screening strategy for HLRCC in women with ULs.
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