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Cell Oncol (Dordr) ; 47(4): 1441-1457, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38564163

RESUMO

PURPOSE: Managing high-grade endometrial cancer in Martinique poses significant challenges. The diversity of copy number alterations in high-grade endometrial tumors, often associated with a TP53 mutation, is a key factor complicating treatment. Due to the high incidence of high-grade tumors with poor prognosis, our study aimed to characterize the molecular signature of these tumors within a cohort of 25 high-grade endometrial cases. METHODS: We conducted a comprehensive pangenomic analysis to categorize the copy number alterations involved in these tumors. Whole-Exome Sequencing (WES) and Homologous Recombination (HR) analysis were performed. The alterations obtained from the WES were classified into various signatures using the Copy Number Signatures tool available in COSMIC. RESULTS: We identified several signatures that correlated with tumor stage and disctinct prognoses. These signatures all seem to be linked to replication stress, with CCNE1 amplification identified as the primary driver of oncogenesis in over 70% of tumors analyzed. CONCLUSION: The identification of CCNE1 amplification, which is currently being explored as a therapeutic target in clinical trials, suggests new treatment strategies for high-grade endometrial cancer. This finding holds particular significance for Martinique, where access to care is challenging.


Assuntos
Ciclina E , Variações do Número de Cópias de DNA , Neoplasias do Endométrio , Amplificação de Genes , Gradação de Tumores , Proteínas Oncogênicas , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Humanos , Ciclina E/genética , Proteínas Oncogênicas/genética , Variações do Número de Cópias de DNA/genética , Carcinogênese/genética , Pessoa de Meia-Idade , Sequenciamento do Exoma , Replicação do DNA/genética , Prognóstico , Idoso
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