多区域外显子组测序表明食管纺锤形细胞鳞状细胞癌起源于单克隆。

IF 5.6 2区医学 Q1 ONCOLOGY

The Journal of Pathology Pub Date : 2024-07-18 DOI:10.1002/path.6324

Yulu Wang, Qian Zhu, Yaqing Wu, Boyi Li, Xiaoxing Su, Chan Xiang, Yuchen Han

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引用次数: 0

摘要

食管纺锤形细胞鳞状细胞癌（ESS）是一种罕见的双相肿瘤，由癌变成分（CaC）和肉瘤成分（SaC）组成。然而，ESS 的基因组起源和基因特征仍不清楚。通过对激光捕获显微切割（LCM）肿瘤样本进行全外显子组测序，我们确定CaC和SaC显示出高度的突变共性，具有相同的顶级高频突变基因、突变特征和肿瘤突变负荷；配对样本共享中位25.5%的突变位点。在染色体3q29、5p15.33和11q13.3上发现了灶性增益。改变的基因主要集中在RTK-RAS信号通路。系统发生树显示ESS起源于单克隆。主干中最常突变的癌基因是TP53，其次是NFE2L2、KMT2D和MUC16。CDC27、LRP2、APC和SNAPC4与预后相关。我们的数据突显了ESS的单克隆起源，TP53是一个强大的驱动癌基因，这表明新的靶向疗法和免疫疗法是治疗的选择。© 2024 大不列颠及爱尔兰病理学会。

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Multiregion exome sequencing indicates a monoclonal origin of esophageal spindle-cell squamous cell carcinoma

Esophageal spindle-cell squamous cell carcinoma (ESS) is a rare biphasic neoplasm composed of a carcinomatous component (CaC) and a sarcomatous component (SaC). However, the genomic origin and gene signature of ESS remain unclear. Using whole-exome sequencing of laser-capture microdissection (LCM) tumor samples, we determined that CaC and SaC showed high mutational commonality, with the same top high-frequency mutant genes, mutation signatures, and tumor mutation burden; paired samples shared a median of 25.5% mutation sites. Focal gains were found on chromosomes 3q29, 5p15.33, and 11q13.3. Altered genes were mainly enriched in the RTK–RAS signaling pathway. Phylogenetic trees showed a monoclonal origin of ESS. The most frequently mutated oncogene in the trunk was TP53, followed by NFE2L2, KMT2D, and MUC16. Prognostic associations were found for CDC27, LRP2, APC, and SNAPC4. Our data highlight the monoclonal origin of ESS with TP53 as a potent driver oncogene, suggesting new targeted therapies and immunotherapies as treatment options. © 2024 The Pathological Society of Great Britain and Ireland.

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来源期刊

The Journal of Pathology 医学-病理学

CiteScore

14.10

自引率

1.40%

发文量

144

审稿时长

3-8 weeks

期刊介绍： The Journal of Pathology aims to serve as a translational bridge between basic biomedical science and clinical medicine with particular emphasis on, but not restricted to, tissue based studies. The main interests of the Journal lie in publishing studies that further our understanding the pathophysiological and pathogenetic mechanisms of human disease. The Journal of Pathology welcomes investigative studies on human tissues, in vitro and in vivo experimental studies, and investigations based on animal models with a clear relevance to human disease, including transgenic systems. As well as original research papers, the Journal seeks to provide rapid publication in a variety of other formats, including editorials, review articles, commentaries and perspectives and other features, both contributed and solicited.