拷贝数特征和 CCNE1 扩增揭示了复制压力在高级别子宫内膜肿瘤发生过程中的作用。

IF 4.9 2区 医学 Q2 CELL BIOLOGY Cellular Oncology Pub Date : 2024-08-01 Epub Date: 2024-04-02 DOI:10.1007/s13402-024-00942-w
Regine Marlin, Jean-Samuel Loger, Clarisse Joachim, Coralie Ebring, Guillaume Robert-Siegwald, Sabrina Pennont, Mickaelle Rose, Kevin Raguette, Valerie Suez-Panama, Sylviane Ulric-Gervaise, Sylvie Lusbec, Odile Bera, Alexis Vallard, Aude Aline-Fardin, Emeline Colomba, Mehdi Jean-Laurent
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引用次数: 0

摘要

目的:在马提尼克岛治疗高级别子宫内膜癌是一项重大挑战。高级别子宫内膜肿瘤拷贝数改变的多样性(通常与 TP53 突变有关)是导致治疗复杂化的一个关键因素。由于预后不良的高级别肿瘤发病率较高,我们的研究旨在对25例高级别子宫内膜癌病例进行分子特征描述:我们进行了全面的泛基因组学分析,对这些肿瘤中涉及的拷贝数改变进行了分类。我们进行了全外显子组测序(WES)和同源重组(HR)分析。利用 COSMIC 中的拷贝数特征工具将从 WES 中获得的改变归类为各种特征:结果:我们发现了几个与肿瘤分期和不同预后相关的特征。这些特征似乎都与复制压力有关,在超过70%的肿瘤分析中,CCNE1扩增被确定为肿瘤发生的主要驱动因素:结论:CCNE1扩增目前正在临床试验中作为治疗靶点进行探索,它的发现为高分化子宫内膜癌提供了新的治疗策略。这一发现对于医疗条件艰苦的马提尼克岛具有特别重要的意义。
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Copy number signatures and CCNE1 amplification reveal the involvement of replication stress in high-grade endometrial tumors oncogenesis.

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.

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来源期刊
Cellular Oncology
Cellular Oncology ONCOLOGY-CELL BIOLOGY
CiteScore
10.30
自引率
1.50%
发文量
86
审稿时长
12 months
期刊介绍: The Official Journal of the International Society for Cellular Oncology Focuses on translational research Addresses the conversion of cell biology to clinical applications Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions. A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients. In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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