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The Morphologic and Molecular Heterogeneity of Fumarate Hydratase-deficient Leiomyomas: Integrative Molecular Profiling of Uterine Smooth Muscle Tumors With Histologic Feature Correlation.
Int J Gynecol Pathol
January 2025
Departments of Pathology.
The morphologic features of uterine smooth muscle tumors (USMTs) are subject to interobserver variability and are complicated by consideration of features of fumarate hydratase deficiency (FHd) and other morphologic subtypes, with difficult cases occasionally diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP). We compare immunohistochemical findings and detailed morphologic analysis of 45 USMTs by 4 fellowship-trained gynecologic pathologists with comprehensive molecular analysis, focusing on FHd leiomyomas (n=15), compared to a variety of other USMTs with overlapping morphologic features, including 9 STUMPs, 8 usual-type leiomyomas (ULM), 11 apoplectic leiomyomas, and 2 leiomyomas with bizarre nuclei (LMBN). FHd leiomyomas, defined by immunohistochemical (IHC) loss of FH and/or 2SC accumulation, showed FH mutations and/or FH copy loss in all cases, with concurrent TP53 mutations in 2 tumors.
View Article and Find Full Text PDFProspective Fumarate Hydratase Tumor Predisposition Syndrome Screening in Patients With Uterine Smooth Muscle Tumors: Age, Morphology, Fumarate Hydratase/S-(2-succino) Cysteine Immunohistochemistry, and Germline Testing.
Am J Surg Pathol
January 2025
Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver BC, Canada.
Fumarate hydratase tumor predisposition syndrome (FHTPS) is caused by germline fumarate hydratase (FH) pathogenic variants (PVs). Most women with FHTPS develop FH-deficient (FHD) uterine leiomyomas (ULs), which arise 10 to 15 years earlier than aggressive FHD-renal cell carcinoma. We evaluate a previously proposed FHTPS screening strategy for women with ULs.
View Article and Find Full Text PDFMetastasis causes most cancer deaths and reflects transitions from primary tumor escape to seeding and growth at metastatic sites. Epithelial-to-mesenchymal transition (EMT) is important early in metastasis to enable cancer cells to detach from neighboring cells, become migratory, and escape the primary tumor. While different phases of metastasis expose cells to variable nutrient environments and demands, the metabolic requirements and plasticity of each step are uncertain.
View Article and Find Full Text PDFAberrant fumarate metabolism links interferon release in diffuse systemic sclerosis.
J Dermatol Sci
January 2025
Biosciences Department, Durham University, Durham, United Kingdom. Electronic address:
Background: Systemic Sclerosis (SSc) is an idiopathic rheumatic inflammatory disease that is characterised by inflammation and skin fibrosis. Type I interferon is significantly elevated in the disease.
Objective: The objective of this study is to determine the role of the TCA cycle metabolite fumarate in SSc.
Addressing genome scale design tradeoffs in Pseudomonas putida for bioconversion of an aromatic carbon source.
NPJ Syst Biol Appl
January 2025
The Joint BioEnergy Institute, Lawrence Berkeley National Laboratory, Emeryville, CA, 94608, USA.
Genome-scale metabolic models (GSMM) are commonly used to identify gene deletion sets that result in growth coupling and pairing product formation with substrate utilization and can improve strain performance beyond levels typically accessible using traditional strain engineering approaches. However, sustainable feedstocks pose a challenge due to incomplete high-resolution metabolic data for non-canonical carbon sources required to curate GSMM and identify implementable designs. Here we address a four-gene deletion design in the Pseudomonas putida KT2440 strain for the lignin-derived non-sugar carbon source, p-coumarate (p-CA), that proved challenging to implement.
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