ArticleInternational journal of clinical and experimental pathology2019
Mutational landscape implicates epithelial-mesenchymal transition gene TGF-β2 mutations for uterine carcinosarcoma after adjuvant tamoxifen therapy for breast carcinoma.
Article in International journal of clinical and experimental pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Feasibility IB trial of paclitaxel/carboplatin + Galunisertib. (a small molecule inhibitor of the kinase domain of type 1 TGF-B receptor) in patients with newly diagnosed, persistent or recurrent carcinosarcoma of the uterus or ovary.Gynecologic oncology · 2025Article
- Carcinosarcoma of the Endometrium-Pathology, Molecular Landscape and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uterine carcinosarcoma (UCS) is a rare aggressive malignancy. Several reports previously described UCS occurring after tamoxifen therapy for breast carcinoma. However, the genetic landscape of tamoxifen-related UCS remains unclear. We performed whole-exome sequencing of two UCSs after tamoxifen therapy for breast carcinoma to determine mutational profile of UCSs and those corresponding breast carcinomas. Our results demonstrated that 374 somatic variants in 141 genes were shared across the two UCSs, whereas no shared somatic variations across the breast carcinomas were found. Pathway analysis indicated the MAPK pathway, including the epithelial-mesenchymal transition (EMT) inducer gene TGF-β2 mutations (c. 1039G > A and c. 1040C > T, both p.A347T), recurrently occurred in UCS, while ER-related gene EP300 (p.P16L) and ESR1 (p.V355I) mutations were identified independently in breast carcinomas. These findings highlight the EMT-related gene TGF-β2 variants in the tumorigenesis of tamoxifen-related UCS, support the possibility that tamoxifen mediates its effect on UCS by enhancing mutations of driver genes, and also provides the rationale for clinical investigation in ER-related gene mutation in breast carcinoma to predict the risk for UCS after tamoxifen treatment.
Indexed as
Identifiers
31933910PMC6945146W3005666539What OpenQuestion holds
Registered trials
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